| 1. |
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| 2. |
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| 3. |
- Bäckhed, Fredrik, 1973, et al.
(författare)
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Structural requirements for TLR4-mediated LPS signalling: a biological role for LPS modifications
- 2003
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Ingår i: Microbes Infect. - 1286-4579 .- 1769-714X. ; 5:12, s. 1057-63
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Tidskriftsartikel (refereegranskat)abstract
- Cells of the mucosal lining are the first to encounter invading bacteria during infection, and as such, they have developed numerous ways of detecting microbial intruders. Recently, we showed that epithelial cells recognize lipopolysaccharide (LPS) through the CD14-Toll-like receptor (TLR)-4 complex. Here, we identify the substructures of LPS that are recognized by the TLR4 receptor complex. In contrast to lipid A, the O-antigen does not mediate an inflammatory response; rather it interferes with the lipid A recognition. An Escherichia coli strain genetically modified to express penta-acylated lipid A not only showed reduced immunogenicity, but was also found to inhibit pro-inflammatory signalling induced by wild-type E. coli (hexa-acylated lipid A) as well as LPS from other bacteria of the Enterobacteriaceae family. Furthermore, penta-acylated LPS from Pseudomonas aeruginosa acted as an antagonist to hexa-acylated E. coli LPS, as did E. coli, as shown by its inhibitory effect on IL-8 production in stimulated cells. Hypo-acylated lipid A, such as that of P. aeruginosa, is found in several species within the gut microflora as well as in several bacteria causing chronic infections. Thus, our results suggest that the composition of the microflora may be important in modulating pro-inflammatory signalling in epithelial cells under normal as well as pathologic conditions.
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| 4. |
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| 5. |
- Gjertsson, Inger, 1962, et al.
(författare)
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Impact of transcription factors AP-1 and NF-kappaB on the outcome of experimental Staphylococcus aureus arthritis and sepsis.
- 2001
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Ingår i: Microbes and infection. - 1286-4579. ; 3:7, s. 527-34
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus infection is, despite adequate antibiotic treatment, a disease characterized by high mortality. The bacterium triggers an exaggerated immune response in the host, which on the one hand acts as an efficient defense, but on the other hand gives rise to tissue damage. In this study we have modulated the hosts response to S. aureus by inhibition of nuclear factor kappaB (NF-kappaB) and activator protein-1 (AP-1)-triggered release of pro-inflammatory cytokines and tissue-destructive proteins, respectively. Mice were administered with antisense oligonucleotides (ODN) to the p65 subunit of NF-kappaB and/or a double-stranded oligonucleotide (mCoAP-1) with homology to the murine AP-1 binding site of collagenase IV gene (metalloproteinase-9; MMP-9), solely or in combination with antibiotics. In mice systemically treated with antisense ODN to NF-kappaB p65 alone, the bacterial burden in the kidneys was significantly increased (P = 0.04) The same tendency was seen when mCoAP-1 was administered either alone or in combination with antibiotics. We also found significantly (P = 0.04) elevated levels of IL-6 in p65 antisense treated mice. Surprisingly, this p65 antisense therapy approach, which has turned out to be highly efficient in amelioration of aseptic arthritis and colitis, failed to change the clinical course of either septic arthritis or sepsis. We suggest that interaction with transcription factors leads to increased bacterial burden in vivo, abrogating the potential benefits of the anti-inflammatory properties exerted by these compounds.
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| 6. |
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| 7. |
- Kraal, G, et al.
(författare)
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The macrophage receptor MARCO
- 2000
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Ingår i: Microbes and infection. - 1286-4579. ; 2:3, s. 313-316
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Tidskriftsartikel (refereegranskat)
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| 8. |
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| 9. |
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| 10. |
- Verdrengh, M, et al.
(författare)
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Integrin-associated protein (IAP)-deficient mice are less susceptible to developing Staphylococcus aureus induced arthritis
- 1999
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Ingår i: Microbes and infection. - 1286-4579 .- 1769-714X. ; 1:10, s. 745-751
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Tidskriftsartikel (refereegranskat)abstract
- The integrin-associated protein (IAP) has been shown to function in a signaling complex with β3 integrins, influencing the migration of phagocytic cells into inflamed tissues. We have previously shown that gene-targeted mice deficient for IAP succumbed to peritonitis when inoculated with Gram-negative bacteria. The aim of this study was to assess the role of IAP in our recently established model of haematogenously induced Staphylococcus aureus septicaemia and arthritis. In this model, neutrophils play a crucial role in the early phase of the infection. Mice lacking IAP and congenic controls were intravenously inoculated with S. aureus LS-1. The IAP-/- mice were resistant to developing clinical signs of arthritis compared with their IAP-expressing littermates. The clinical findings were corroborated by histopathological evaluation indicating that the IAP-/- mice had less cartilage and bone destruction in the joints. We believe that a delayed migration of leukocytes into the joints of mice lacking IAP expression leads to decreased susceptibility to develop S. aureus-induced arthritis.
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| 11. |
- Ahrné, Siv, et al.
(författare)
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Lactobacilli in the intestinal microbiota of Swedish infants
- 2005
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Ingår i: Microbes and Infection. - : Elsevier BV. - 1286-4579 .- 1769-714X. ; 7:11-12, s. 1256-62
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Tidskriftsartikel (refereegranskat)abstract
- Lactobacillus colonisation was examined in 112 Swedish infants. Faecal samples obtained at 1, 2, 4 and 8 weeks and at 6, 12 and 18 months of age were cultivated quantitatively on Rogosa agar. Lactobacilli were speciated by PCR and typed to the strain level by randomly amplified polymorphic DNA (RAPD). Lactobacilli reached a peak at 6 months when 45% of the infants were colonised. L. rhamnosus and L. gasseri were the most common species in this period. Colonisation by lactobacilli in general (P < 0.01) and L. rhamnosus in particular (P < 0.05) was more common in breast-fed than in weaned infants at 6 months of age. Lactobacillus isolation reached a nadir of 17% by 12 months (P < 0.0001), but increased to 31% by 18 months of age P < 0.05). The food-related species L. paracasei, L. plantarum, L. acidophilus and L. delbrueckii dominated in this second phase. A single strain persisted for at least 3 weeks in 17% of the infants during the first 6 months, most commonly L. rhamnosus. Lactobacillus population counts in colonised infants increased from 10(6.4) cfu/g at 1 week to 10(8.8) cfu/g at 6 months, and then dropped to 10(5.4) cfu/g faeces at 12 months of age. Lactobacillus colonisation was not significantly related to delivery mode, or to presence of siblings or pets in the household. Our results suggest that certain Lactobacillus species, especially L. rhamnosus, thrive in the intestinal flora of breast-fed infants. After weaning they are replaced by other Lactobacillus species of types found in food.
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| 12. |
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| 13. |
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| 14. |
- Barkman, Cecilia, 1962, et al.
(författare)
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Soluble bacterial constituents down-regulate secretion of IL-12 in response to intact Gram-positive bacteria.
- 2008
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Ingår i: Microbes and infection / Institut Pasteur. - : Elsevier BV. - 1286-4579. ; 10:14-15, s. 1484-93
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Tidskriftsartikel (refereegranskat)abstract
- Intact Gram-positive bacteria induce production of large amounts of IL-12 from freshly isolated human monocytes. Here the bacterial structures and signalling pathways involved were studied and compared with those leading to IL-6 production, and to IL-12 production in response to LPS after IFN-gamma pre-treatment. Intact bifidobacteria induced massive production of IL-12 (1ng/ml) and IL-6 (>30ng/ml) from human PBMC, whereas fragmented bifidobacteria induced IL-6, but no IL-12. IL-12 production induced by intact bifidobacteria was inhibited by pre-treatment with bifidobacterial sonicate, peptidoglycan, muramyl dipeptide, lipoteichoic acid, the soluble TLR2 agonist Pam(3)Cys-SK(4), or anti-TLR2 antibodies. Blocking of phagocytosis by cytochalasin, inhibition of the JNK or NF-kappaB pathways or treatment with Wortmannin also reduced the IL-12 response to intact Gram-positive bacteria. LPS induced moderate levels of IL-12 (0.31ng/ml), but only from IFN-gamma pre-treated PBMC. This IL-12 production was enhanced by Wortmannin and unaffected by blocking the JNK pathway. Thus, intact Gram-positive bacteria trigger monocyte production of large amounts of IL-12 via a distinct pathway that is turned off by fragmented Gram-positive bacteria. This may be a physiological feedback, since such fragments may signal that further activation of the phagocyte via the IL-12/IFN-gamma loop is unnecessary.
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| 15. |
- Bereczky, Sándor, et al.
(författare)
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Multiclonal asymptomatic Plasmodium falciparum infections predict a reduced risk of malaria disease in a Tanzanian population
- 2007
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Ingår i: Microbes and infection. - : Elsevier BV. - 1286-4579 .- 1769-714X. ; 9:1, s. 103-110
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Tidskriftsartikel (refereegranskat)abstract
- Protective immunity to malaria is acquired after repeated exposure to the polymorphic Plasmodium falciparum parasite. Whether the number of concurrent antigenically diverse clones in asymptomatic infections predicts the risk of subsequent clinical malaria needs further understanding. We assessed the diversity of P. falciparum infections by merozoite surface protein 2 genotyping in a longitudinal population based study in Tanzania. The number of clones was highest in children 6–10 years and in individuals with long time to previous anti-malarial treatment. Individual exposure, analysed by circumsporozoite protein antibody levels, was associated with parasite prevalence but not with the number of clones. The risk of subsequent clinical malaria in children free of acute disease or recent treatment was, compared to one clone, reduced in individuals with multiclonal infections or without detectable parasites, with the lowest hazard ratio 0.28 (95% confidence interval 0.10–0.78 Cox regression) for 2–3 clones. The number of clones was not associated with haemoglobin levels. A reduced risk of malaria in asymptomatic individuals with multiclonal persistent P. falciparum infections suggests that controlled maintenance of diverse infections is important for clinical protection in continuously exposed individuals, and needs to be considered in the design and evaluation of new malaria control strategies.
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| 16. |
- Berglund, Carolina, et al.
(författare)
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The genes for Panton Valentine leukocidin (PVL) are conserved in diverse lines of methicillin-resistant and methicillin-susceptible Staphylococcus aureus
- 2008
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Ingår i: Microbes and infection. - Paris : Elsevier. - 1286-4579 .- 1769-714X. ; 10:8, s. 878-884
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Methicillin-resistant Staphylococcus aureus isolated in the community (CA-MRSA) have been reported to carry the loci for Panton Valentine leukocidin (PVL) in high frequency. CA-MRSA in Orebro County, Sweden, constitutes at least 50% of MRSA and the PVL locus is detected in as many as 66% of these CA-MRSA isolates. The aim of this study was to characterize PVL-positive methicillin-resistant and methicillin-susceptible Staphylococcus aureus by molecular methods, to determine the nucleotide sequence of lukS-PV and lukF-PV in S. aureus isolates of different origins, and to investigate the biological consequence of variations occurring in the genes. The PVL-positive MRSA investigated were composed of six different STs (ST8, 36, 80, 152, 154, and 256). Six additional STs (ST5, 22, 25, 30, 88, and 567) were detected when investigating PVL-positive methicillin-susceptible S. aureus with MLST. Despite the different genetic origins of the isolates analyzed, the PVL genes were well conserved and only one mutation was non-synonymous. Evaluation of the consequence of this mutation showed that the mutated toxin and wild-type toxin had comparable biological activity on human polymorphonuclear cells.
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| 17. |
- Bhuiyan, T. R., et al.
(författare)
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Assessing antigen specific HLA-DR plus antibody secreting cell (DR plus ASC) responses in whole blood in enteric infections using an ELISPOT technique
- 2018
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Ingår i: Microbes and Infection. - : Elsevier BV. - 1286-4579. ; 20:2, s. 122-129
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Tidskriftsartikel (refereegranskat)abstract
- Antibody secreting cells (ASCs) generate antibodies in an antigen-specific manner as part of the adaptive immune response to infections, and these cells increase their surface expression of HLA-DR. We have studied this parameter (HLA-DR+ASC) in patients with recent diarrheal infection using immuno-magnetic cell sorting and an enzyme linked immunospot (ELISPOT) technique that requires only one milliliter of blood. We validated this approach in adult patients with cholera (n = 15) or ETEC diarrhea (n = 30) on days 2, 7 and 30 after showing clinical symptom at the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr, b) hospital in Dhaka, and we compared responses to age-matched healthy controls (n = 7). We found that HLA-DRthorn ASC (DR+ASC) responses specific both for T cell-dependent (cholera toxin B subunit), and T cell-independent (lipopolysaccharide) antigens were elevated at day 7 after showing clinical cholera symptom. Similarly, DR+ASCs were elevated against both heat-labile toxin and colonization factors following ETEC infection. We observed significant correlations between antigen-specific DR+ASC responses and antigen-specific, gut homing ASC and plasma antibody responses. This study demonstrates that a simple ELISPOT procedure allows determination of antigen-specific ASC responses using a small volume of whole blood following diarrhea. This technique may be particularly useful in studying DR+ASC responses in young children and infants, either following infection or vaccination. (c) 2017 The Authors. Published by Elsevier Masson SAS on behalf of Institut Pasteur.
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| 18. |
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| 19. |
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| 20. |
- Calander, Ann-Marie, 1957, et al.
(författare)
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Impact of staphylococcal protease expression on the outcome of infectious arthritis
- 2004
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Ingår i: Microbes Infect. - : Elsevier BV. - 1286-4579. ; 6:2, s. 202-6
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Tidskriftsartikel (refereegranskat)abstract
- The exoproteases of Staphylococcus aureus have been proposed as virulence factors during S. aureus infections. To investigate this, we used the wild-type S. aureus strain 8325-4 and its mutants devoid of aureolysin, serine protease, and cysteine protease, respectively, in a well-established model of septic arthritis in mice. The inactivation of the exoprotease genes did not affect the frequency or the severity of joint disease. We conclude that in the model of haematogenously spread staphylococcal arthritis, the bacterial proteases studied do not act as virulence factors.
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| 21. |
- Calander, Ann-Marie, 1957, et al.
(författare)
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Matrix metalloproteinase-9 (gelatinase B) deficiency leads to increased severity of Staphylococcus aureus-triggered septic arthritis.
- 2006
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Ingår i: Microbes and infection / Institut Pasteur. - : Elsevier BV. - 1286-4579. ; 8:6, s. 1434-9
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Tidskriftsartikel (refereegranskat)abstract
- Matrix metalloproteinases constitute a family of structurally related endopeptidases that are crucial for the normal turnover of the extracellular matrix. Elevated levels of MMP-9 have been demonstrated in synovial fluids of rheumatoid arthritis patients, and a correlation with the severity of the disease has been described. The aim of this study was to explore the impact of MMP-9 expression on joint inflammation and destruction in a model of bacterially induced septic arthritis. MMP-9 knock-out mice and C57Bl6 congenic controls were inoculated intravenously or intra-articularly with Staphylococcus aureus. Arthritis was evaluated clinically and by means of histology. Zymographic analyses were performed to study ex vivo induction of MMP-9 following exposure to S. aureus. The MMP-9 knock-out mice displayed a significantly higher frequency and severity, but not destructivity, of arthritis than did the wild-type mice. The knock-out mice also proved to harbour an increased number of bacteria locally in joints and systemically in kidneys, possibly by impaired extravasation and recruitment of leukocytes and a deficient early defence against infection. Our findings indicate that deficiency in MMP-9 increases the degree of joint inflammation due to decreased bacterial clearance.
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| 22. |
- Carroll, R. K., et al.
(författare)
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Identification of an intracellular M17 family leucine aminopeptidase that is required for virulence in Staphylococcus aureus
- 2012
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Ingår i: Microbes and Infection. - : Elsevier BV. - 1286-4579. ; 14:11, s. 989-999
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus is a highly virulent bacterial pathogen capable of causing a variety of ailments throughout the human body. It is a major public health concern due to the continued emergence of highly pathogenic methicillin resistant strains (MRSA) both within hospitals and in the community. Virulence in S. aureus is mediated by an array of secreted and cell wall associated virulence factors, including toxins, hemolysins and proteases. In this work we identify a (l) under bar eucine (a) under bar mino (p) under bar eptidase (LAP, pepZ) that strongly impacts the pathogenic abilities of S. aureus. Disruption of the pepZ gene in either Newman or USA300 resulted in a dramatic attenuation of virulence in both localized and systemic models of infection. LAP is required for survival inside human macrophages and gene expression analysis shows that pepZ expression is highest in the intracellular environment. We examine the cellular location of LAP and demonstrate that it is localized to the bacterial cytosol. These results identify for the first time an intracellular leucine aminopeptidase that influences disease causation in a Gram-positive bacterium. (C) 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
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| 23. |
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| 24. |
- Charpentier, E, et al.
(författare)
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Mechanisms of antibiotic resistance and tolerance in Streptococcus pneumoniae.
- 2000
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Ingår i: Microbes and infection. - 1286-4579 .- 1769-714X. ; 2:15, s. 1855-64
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pneumoniae is a major pathogen causing potentially life-threatening community-acquired diseases in both the developed and developing world. Since 1967, there has been a dramatic increase in the incidence of penicillin-resistant and multiply antibiotic-resistant pneumococci worldwide. Prevention of access of the antibiotic to the target, inactivation of the antibiotic and alteration of the target are mechanisms that S. pneumoniae has developed to resist antibiotics. Recent studies on antibiotic-tolerant pneumococcal mutants permitted development of a novel model for the control of bacterial cell death.
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| 25. |
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| 26. |
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| 27. |
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| 28. |
- Edqvist, Petra J, et al.
(författare)
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Minimal YopB and YopD translocator secretion by Yersinia is sufficient for Yop-effector delivery into target cells.
- 2007
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Ingår i: Microbes and infection. - : Elsevier BV. - 1286-4579 .- 1769-714X. ; 9:2, s. 224-233
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Tidskriftsartikel (refereegranskat)abstract
- Pathogenic Yersinia sp. utilise a common type III secretion system to translocate several anti-host Yop effectors into the cytosol of target eukaryotic cells. The secreted YopB and YopD translocator proteins are essential for this process, forming pores in biological membranes through which the effectors are thought to gain access to the cell interior. The non-secreted cognate chaperone, LcrH, also plays an important role by ensuring pre-secretory stabilisation and efficient secretion of YopB and YopD. This suggests that LcrH-regulated secretion of the translocators could be used by Yersinia to control effector translocation levels. We collected several LcrH mutants impaired in chaperone activity. These poorly bound, stabilised and/or secreted YopB and YopD in vitro. However, these mutants generally maintained stable substrates during a HeLa cell infection and these infected cells were intoxicated by translocated effectors. Surprisingly, this occurred in the absence of detectable YopB- and YopD-dependent pores in eukaryotic membranes. A functional type III translocon must therefore only require minuscule amounts of secreted translocator proteins. Based on these observations, LcrH dependent control of translocation via regulated YopB and YopD secretion would need to be exquisitely tight.
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| 29. |
- Ehrström, Sophia, et al.
(författare)
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Lactic acid bacteria colonization and clinical outcome after probiotic supplementation in conventionally treated bacterial vaginosis and vulvovaginal candidiasis
- 2010
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Ingår i: Microbes and infection. - : Elsevier BV. - 1286-4579 .- 1769-714X. ; 12:10, s. 691-699
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Tidskriftsartikel (refereegranskat)abstract
- This randomized double-blind placebo controlled study assessed the vaginal colonization of lactic acid bacteria and clinical outcome. Vaginal capsules containing L gasseri LN40, Lactobacillus fermentum LN99, L. casei subsp. rhamnosus LN113 and P. acidilactici LN23, or placebos were administered for five days to 95 women after conventional treatment of bacterial vaginosis and/or vulvovaginal candidiasis. Vulvovaginal examinations and vaginal samplings were performed before and after administration, after the first and second menstruation, and after six months. Presence of LN strains was assessed using RAPD analysis. LN strains were present 2-3 days after administration in 89% of the women receiving LN strains (placebo: 0%, p < 0.0001). After one menstruation 53% were colonized by at least one LN strain. Nine percent were still colonized six months after administration. Ninety-three percent of the women receiving LN strains were cured 2-3 days after administration (placebo: 83%), and 78% after one menstruation (placebo: 71%) (ns). The intervention group experienced less malodorous discharge 2-3 days after administration (p = 0.03) and after the second menstruation (p = 0.04), compared with placebo. In summary, five days of vaginal administration of LN strains after conventional treatment of bacterial vaginosis and/or vulvovaginal candidiasis lead to vaginal colonization, somewhat fewer recurrences and less malodorous discharge.
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| 30. |
- Eliasson, Mette, et al.
(författare)
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Streptococcus pneumoniae induces expression of the antibacterial CXC chemokine MIG/CXCL9 via MyD88-dependent signaling in a murine model of airway infection.
- 2010
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Ingår i: Microbes and Infection. - : Elsevier BV. - 1769-714X .- 1286-4579. ; 12, s. 565-573
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Tidskriftsartikel (refereegranskat)abstract
- MIG/CXCL9 belongs to the CXC family of chemokines and participates in the regulation of leukocyte-trafficking and angiogenesis. Certain chemokines, including human MIG/CXCL9, exert strong antibacterial activity in vitro, although the importance of this property in vivo is unknown. In the present study, we investigated the expression and a possible role for MIG/CXCL9 in host defense during mucosal airway infection caused by Streptococcus pneumoniae in vivo. We found that intranasal challenge of C57BL/6 wild-type mice with pneumococci elicited production of high levels of MIG/CXCL9 in the lungs via the MyD88-dependent signaling pathway. Whereas both human and murine MIG/CXCL9 showed efficient killing of S. pneumoniae in vitro, MIG/CXCL9 knock-out mice were not more susceptible to pneumococcal infection. Our data demonstrate that, in vivo this chemokine probably has a redundant role, acting together with other antibacterial peptides and chemokines, in innate and adaptive host defense mechanisms against pneumococcal infections.
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| 31. |
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| 32. |
- Farouk, Salah E., et al.
(författare)
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Different antibody and cytokine-mediated responses to Plasmodium falciparum parasite in two sympatric ethnic tribes living in Mali
- 2005
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Ingår i: Microbes and infection. - : Elsevier SAS. - 1286-4579 .- 1769-714X. ; 7:1, s. 110-117
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Tidskriftsartikel (refereegranskat)abstract
- The Fulani are known to be less susceptible to Plasmodium falciparum malaria infections and to have lower parasitaemia despite living under similar malaria transmission intensity compared with other ethnic tribes. The aim of the present study was to examine whether the Fulani were more polarised towards Th2 as reflected by higher numbers of malaria-specific IL-4- and IL-10-producing cells and lower numbers of IFN-γ- and IL-12-producing cells as compared to their neighbour ethnic tribe, the Dogon of Mali. Total IgE and both anti-malaria IgE and IgG antibodies were measured by ELISA and the numbers of IL-4-, IFN-γ-, IL-10- and IL-12-producing cells were enumerated using enzyme-linked ImmunoSpot assay (ELISPOT). Numbers of parasite clones were detected by polymerase chain reaction (PCR). The study was performed outside the transmission period and all individuals included were asymptomatic. The results revealed that the Fulani were less parasitised, had fewer circulating parasite clones in their blood, had significantly higher anti-malaria IgG and IgE antibodies and higher proportions of malaria-specific IL-4- and IFN-γ-producing cells compared to the Dogon. The higher antigen-specific production of IL-4 among the Fulani was statistically significant both before and after adjustment for level of spontaneous cytokine production, while greater IFN-γ production only attained statistical significance after adjustment for spontaneous levels. Taken together, the association of higher anti-malarial IgE and IgG antibodies and increased numbers of specific IL-4- and IFN-γ-producing cells compared to the ethnic sympatric tribe, the Dogon, may assist in explaining the lower susceptibility to malaria observed in the Fulani.
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| 33. |
- Fäldt, Jenny, 1971, et al.
(författare)
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Priming of human neutrophils by mycobacterial lipoarabinomannans: role of granule mobilisation.
- 2001
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Ingår i: Microbes and infection. - 1286-4579. ; 3:13, s. 1101-9
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Tidskriftsartikel (refereegranskat)abstract
- Lipoarabinomannans (LAMs) from mycobacteria were investigated concerning their effect on human neutrophils. Two types of LAM, the mannose-capped ManLAM from the virulent Mycobacterium tuberculosis H37Rv and the mannose-lacking AraLAM from a rapidly growing mycobacterial strain were used. Neither AraLAM nor ManLAM induced any significant direct activation of the NADPH-oxidase. Both LAMs, however, primed the neutrophils so that subsequent stimulation with the peptide chemoattractants fMet-Leu-Phe (fMLF), Trp-Lys-Tyr-Met-Val-DMet (WKYMVm) and the mammalian lactose-binding lectin galectin-3 resulted in a markedly enhanced oxidative response. The LAM-induced priming was accompanied by an increased exposure of complement receptors 1 and 3 as well as the formyl peptide receptor on the neutrophil surface, suggesting that the enhanced oxidative response could be due to upregulation of receptors on the cell surface as a result of granule mobilisation. Since LAM-primed neutrophils released 65% of the cell content of gelatinase but showed no increased release of vitamin B(12)-binding protein, mobilisation of the gelatinase granules rather than the specific granules is concluded to be responsible for the priming effects. This is in agreement with the subcellular localisation of receptors for fMLF, WKYMVm, as well as galectin-3, which are stored in the secretory vesicles and gelatinase granules. The priming effect appeared very similar to that of Escherichia coli lipopolysaccharide, and since no differences in activity could be detected between AraLAM and ManLAM, we hypothesize that the lipid anchor of the LAM is responsible for the priming effects.
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| 34. |
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| 35. |
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| 36. |
- Giha, Hayder A., et al.
(författare)
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Lack of significant influence for Fc gamma RIIa-RH131 or hemoglobin AA/AS polymorphisms on immunity and susceptibility to uncomplicated malaria and existence of marked linkage between the two polymorphisms in Daraweesh
- 2012
-
Ingår i: Microbes and infection. - : Elsevier BV. - 1286-4579 .- 1769-714X. ; 14:6, s. 537-544
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Tidskriftsartikel (refereegranskat)abstract
- Malaria signature on human genome is marked by several gene polymorphisms. HemoglobinAS (HbAS) is known to protect against severe malaria, but barely proved to protect against uncomplicated malaria (UM). Similarly, the influence of Fc gamma RIIa-RH131 polymorphism on malaria is controversial. Polymorphisms in both genes were examined and levels of IgG subclasses against four malaria antigens were measured for 250 Fulani's from Daraweesh, eastern Sudan. Morbidity data for up to nine years was available for 214 donors. Number of malaria episodes experienced by each individual during the study period was used as indicator for susceptibility to UM. PCR and RFLP were used for donors DNA genotyping and ELISA for antibodies measurement. Results revealed that neither Fc gamma RIIa-RH131 alleles/genotypes nor HbAA/AS was significantly associated with malaria morbidity or with levels of IgG to test antigens. Both polymorphisms were in Hardy-Weinberg Equilibrium, interestingly, there was strong association between the two polymorphisms (linkage disequilibrium - LD) with D' = 0.89. The association between the two polymorphisms was confirmed by analysis of independent material from a neighboring village. In conclusion, in Daraweesh both Fc gamma RIIa-RH131 and HbAA/AS genotypes, independently or together, were not major markers for UM susceptibility, however, marked LD was observed between the two polymorphisms.
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| 37. |
- Gillenius, Erik, et al.
(författare)
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The adhesive protein invasin of Yersinia pseudotuberculosis induces neutrophil extracellular traps via β1 integrins
- 2015
-
Ingår i: Microbes and infection. - : Elsevier BV. - 1286-4579 .- 1769-714X. ; 17:5, s. 327-336
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Tidskriftsartikel (refereegranskat)abstract
- Yersinia pseudotuberculosis adhesive protein invasin is crucial for the bacteria to cross the intestine epithelium by binding to β1 integrins on M-cells and gaining access to the underlying tissues. After the crossing invasin can bind to β1 integrins on other cell surfaces, however effector proteins delivered by the type III secretion system Y. pseudotuberculosis efficiently inhibit potential immune responses induced by this interaction. Here, we use mutant Y. pseudotuberculosis strains lacking the type III secretion system and additionally invasin-expressing Escherichia coli to analyze neutrophil responses towards invasin. Our data reveals that invasin induces production of reactive oxygen species and release of chromatin into the extracellular milieu, which we confirmed to be neutrophil extracellular traps by immunofluorescence microscopy. This was mediated through β1 integrins and was dependent on both the production of reactive oxygen species and signaling through phosphoinositide 3-kinase. We therefore have gained insight into a potential role of integrins in inflammation and infection clearance that has not previously been described, suggesting that targeting of β1 integrins could be utilized as an adjunctive therapy against yersiniosis.
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| 38. |
- Gjertsson, Inger, 1962, et al.
(författare)
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The role of B cell CD22 expression in Staphylococcus aureus arthritis and sepsis
- 2004
-
Ingår i: Microbes Infect. - 1286-4579. ; 6:4, s. 377-82
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Tidskriftsartikel (refereegranskat)abstract
- Severe Staphylococcus aureus infections give rise to a pronounced antigen-specific and polyclonal B cell response with elevated serum immunoglobulin levels. However, it has been difficult to correlate the antibody levels with the clinical outcome of sepsis and/or arthritis concerning both protection and pathogenic aspects. Earlier studies have shown that macrophages and neutrophils are of great importance for bacterial clearance. However, deletion of the complete B cell compartment affected neither S. aureus-induced arthritis nor survival. MZ B cells are believed to be of importance for clearance of blood-borne antigens and have been implicated in protection against S. aureus infections. CD22 is a B-cell-specific inhibitory receptor binding to alpha2,6-linked sialic acids, and deficiency in CD22 leads to a 75% reduction of the MZ B cell compartment. CD22-/- mice and congeneic controls were inoculated intravenously with an arthritogenic dose of live S. aureus. No differences between the groups were detected regarding frequency and severity of arthritis, survival, bacterial clearance, or induction of inflammatory response. This study shows explicitly that a reduced MZ B cell compartment in the absence of CD22 expression does not interfere with the inflammatory response during S. aureus infection.
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| 39. |
- Hallström, Teresia, et al.
(författare)
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The Moraxella IgD-binding protein MID/Hag is an oligomeric autotransporter.
- 2008
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Ingår i: Microbes and Infection. - : Elsevier BV. - 1769-714X .- 1286-4579. ; 10:4, s. 374-381
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Tidskriftsartikel (refereegranskat)abstract
- The immunoglobulin D (IgD)-binding protein MID/Hag of the human respiratory pathogen Moraxella catarrhalis is an outer membrane protein of approximately 200kDa belonging to the autotransporter family. MID also functions as an adhesin and hemagglutinin. In the present paper, the ultrastructure of MID was mapped. Using a series of Escherichia coli transformants, the last 210 aa of the C-terminal region were shown to translocate protein MID through the outer membrane suggesting that MID has a beta-barrel structure comprising of 10 transmembrane beta-sheets. Electron microscopy mapping with gold-labelled specific antibodies, and partial unravelling using guanidine hydrochloride showed that the rest of the MID protein forms an approximately 120nm long, fibrillar structure in which the individual monomers fold back on themselves to expose a globular distal domain at their tips comprising both the IgD-binding (MID962-1200) and adhesive (MID764-913) regions. This positions their N-termini close to the C-terminal membrane spanning domains. Mass measurements by scanning transmission electron microscopy (STEM) verified that the MID molecule is an oligomer.
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| 40. |
- Hansson, Malin, 1967, et al.
(författare)
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Dendritic cells express CCR7 and migrate in response to CCL19 (MIP-3beta) after exposure to Helicobacter pylori
- 2006
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Ingår i: Microbes Infect. - : Elsevier BV. - 1286-4579. ; 8:3, s. 841-50
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Forskningsöversikt (refereegranskat)abstract
- Helicobacter pylori infection induces chronic inflammation in the gastric mucosa with a marked increase in the number of lymphoid follicles consisting of infiltrating B and T cells, neutrophils, dendritic cells (DC) and macrophages. It has been suggested that an accumulation of mature DC in the tissue, resulting from a failure of DC to migrate to lymph nodes, may contribute to this chronic inflammation. Migration of DC to lymph nodes is regulated by chemokine receptor CCR7, expressed on mature DC, and the CCR7 ligands CCL19 and CCL21. In this study we analysed the maturation, in vitro migration and cytokine production of human DC after stimulation with live H. pylori. For comparison, DC responses to non-pathogenic Escherichia coli bacteria were also evaluated. Stimulation with H. pylori induced maturation of DC, i.e. up-regulation of the chemokine receptors CCR7 and CXCR4 and the maturation markers HLA-DR, CD80 and CD86. The H. pylori-stimulated DC also induced CD4(+) T-cell proliferation. DC stimulated with H. pylori secreted significantly more interleukin (IL)-12 compared to DC stimulated with E. coli, while E. coli-stimulated DC secreted more IL-10. Despite low surface expression of CCR7 protein following stimulation with H. pylori compared to E. coli, the DC migrated equally well towards CCL19 after stimulation with both bacteria. Thus, we could not detect any failure in the migration of H. pylori stimulated DC in vitro that may contribute to chronic gastritis in vivo, and our results suggest that H. pylori induces maturation and migration of DC to lymph nodes where they promote T cell responses.
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| 41. |
- Herrmann, Björn, 1955-, et al.
(författare)
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SNP-based high-resolution typing of Chlamydia psittaci from humans and wild birds in Sweden : circulation of the Mat116 genotype reveals the transmission mode to humans
- 2024
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Ingår i: Microbes and infection. - : Elsevier. - 1286-4579 .- 1769-714X. ; 26:3
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of Chlamydia psittaci respiratory tract infections in humans has increased in Sweden in recent years. This study aimed to identify the transmission route by genotyping C. psittaci from infected humans and birds.42 human C. psittaci samples and 5 samples from C. psittaci-infected birds were collected. Genotyping was performed using ompA sequencing, Multi-locus sequence typing, and/or SNP-based high-resolution melting-PCR. Epidemiological data was also collected, and a phylogenetic analysis was conducted.Analysis of ompA provided limited resolution, while the SNP-based PCR analysis successfully detected the Mat116 genotype in 3/5 passerine birds and in 26/29 human cases, indicating a high prevalence of this genotype in the human population. These cases were associated with contact with wild birds, mainly through bird feeding during winter or other outdoor exposure. Human cases caused by other genotypes (psittacine and pigeon) were less common and were linked to exposure to caged birds or pigeons.The SNP-genotype Mat116 is rare, but predominated in this study. The use of SNP-based PCR provided a better understanding of the C. psittaci transmission from birds to humans compared to ompA analysis. In Sweden, human psittacosis appears mainly to be transmitted from garden birds during bird feeding in the winter season.
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| 42. |
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| 43. |
- Hultgren, Olof H., 1970, et al.
(författare)
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T-box transcription-factor-deficient mice display increased joint pathology and failure of infection control during staphylococcal arthritis.
- 2004
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Ingår i: Microbes and infection / Institut Pasteur. - : Elsevier BV. - 1286-4579. ; 6:6, s. 529-35
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Tidskriftsartikel (refereegranskat)abstract
- To study the impact of T-box transcription factor (T-bet) on initiation and progression of Staphylococcus aureus sepsis and arthritis, T-bet-deficient mice (T-bet(-/-)) and their wild-type controls (T-bet(+/+)) were intravenously inoculated with 8 x 10(6) S. aureus. Already 48 h after inoculation of S. aureus, T-bet-deficient mice displayed increased frequency (62% versus 19%, P = 0.002) as well as severity of arthritis compared with wild-type controls. The bacterial counts were significantly increased in T-bet(-/-) mice compared with T-bet(+/+) as measured in kidneys 72 h after the inoculation (4.3 +/- 1.8 x 10(7) versus 3.2 +/- 3.2 x 10(6) colony-forming units (CFU); P = 0.003). As expected, T-bet-deficient mice displayed significantly decreased production of IFN-gamma (10-15-fold) at 24 and 72 h after bacterial inoculation compared with wild-type mice. Interestingly, in the absence of T-bet, serum IL-4 was decreased at 24 h. IL-6 did not differ at early stage of infection but was sixfold increased in T-bet(-/-) mice over T-bet(+/+) animals at 72 h postinoculation. Ten days after the inoculation, T-bet(-/-) mice still displayed significantly more pronounced weight loss and increased serum IL-6 levels, probably due to increased bacterial burden compared with T-bet(+/+) mice. The cumulative mortality was 19% in T-bet mice (5/27) and 0% (0/27) in control animals (P = 0.05). In conclusion, T-bet plays an important role in early response to S. aureus infection, protecting against bacterial accumulation, cachexia and septic death. Furthermore T-bet downregulates joint inflammation in the early phase of disease.
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| 44. |
- Jangpatarapongsa, Kulachart, et al.
(författare)
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Memory T cells protect against Plasmodium vivax infection
- 2006
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Ingår i: Microbes and infection. - : Elsevier BV. - 1286-4579 .- 1769-714X. ; 8:3, s. 680-686
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Tidskriftsartikel (refereegranskat)abstract
- Immunity induced by Plasmodium vivax infection leads to memory T cell recruitment activated during "relapse" or "re-infection". This study aims to characterise memory T cells in patients with acute or convalescent P. vivax infection. Lymphocytes were collected from patients infected by P. vivax, immune controls and naive controls. The proportion of immature memory T cells, expressing CD45RO(+)CD27(+), and mature cells lacking CD27 was assessed. A statistically significant increase in the median percentage of memory T cell subsets expressing CD4(+) was observed in material from patients with an acute infection compared with that from either naive or immune controls. The high percentage of memory T cells in infected patients was maintained until 60 days post treatment. The immune controls living in a malaria endemic area had a somewhat increased proportion of memory T cell subsets expressing CD8(+). An approximately three-fold increase of these cell types was shown in patients with an acute infection and the level persisted until 60 days post treatment. Phenotypic characterisation of the peripheral lymphocytes during acute infection revealed that a large fraction of the lymphocytes carried the gammadelta phenotypes suggesting a role for these cells in the early response against P. vivax. Very low levels of P. vivax specific antibody were found. This might suggest that cell-mediated immunity may play a greater role in the development of naturally acquired protection against P. vivax infection than humoral immunity. Our results provide further insight into the mechanism of cell-mediated immunity to P. vivax infection that could be important for the future development of a successful vaccine and anti-malarial drug designation.
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| 45. |
- Jin, Tao, 1973, et al.
(författare)
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The role of urokinase in innate immunity against Staphylococcus aureus
- 2005
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Ingår i: Microbes Infect. - : Elsevier BV. - 1286-4579. ; 7:9-10, s. 1170-5
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Tidskriftsartikel (refereegranskat)abstract
- Urokinase (uPA) is a serine protease that not only displays fibrinolytic function but also promotes host leukocytes to home to inflammatory sites. We have recently demonstrated that staphylokinase (SAK), which is a fibrinolytic protein secreted by Staphylococcus aureus, forms complexes with human neutrophil peptides (HNPs), which are members of the defensin family and have anti-microbial properties, thereby inhibiting the bactericidal effects of the HNPs. The aim of this study was to assess whether endogenous uPA, which has fibrinolytic properties similar to those of SAK, binds to HNPs and interferes with SAK/HNPs interaction. To this end, an ELISA was used to analyze the interactions between uPA and HNPs. HMW uPA had the ability to bind to both HNP types. The biological consequences of the formation of this complex were analyzed with respect to its bactericidal properties. HMW uPA killed S. aureus, albeit at relatively high doses (50-100 mug/ml). In contrast, the binding of HMW uPA to HNPs had no impact on the bactericidal functions of the HNPs. Importantly, the addition of HMW uPA to SAK eliminated the ability of SAK to neutralize HNPs. Our results demonstrate that endogenous HMW uPA inhibits S. aureus growth both directly, by cytolysis, and indirectly, by abrogation of the neutralizing effect of SAK on the bactericidal activities of HNPs. These findings indicate novel functions of HMW uPA in the host defense against staphylococcal infections.
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| 46. |
- Jonsson, Ing-Marie, 1949, et al.
(författare)
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mgrA regulates staphylococcal virulence important for induction and progression of septic arthritis and sepsis.
- 2008
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Ingår i: Microbes and infection / Institut Pasteur. - : Elsevier BV. - 1286-4579. ; 10:12-13, s. 1229-35
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Tidskriftsartikel (refereegranskat)abstract
- Septic arthritis and sepsis are common and feared complications of staphylococcal infections, and the increasing antibiotic resistance among staphylococci urge the extended research for virulence factors involved in these diseases. Staphylcoccus aureus produces a number of virulence factors controlled by several global regulatory genes including agr and sarA. MgrA is a recently identified global regulator, belonging to the SarA subfamily, which upregulates expression of several virulence factors including capsule and sortase. In addition, MgrA has been shown to regulate antibiotic resistance and decrease bacterial autolysis. In this study we have assessed the role of mgrA gene expression on induction and progression of septic arthritis and sepsis. Mice inoculated with the mgrA mutant displayed significantly less severe arthritis and showed a significantly better weight development, than wild-type inoculated mice. Importantly, all 10 mice inoculated with the mgrA mutant survived as compared to 70% mortality in the wild-type inoculated mice (p=0.003). In addition, the mgrA mutant showed significantly less bacterial persistence in kidneys as compared to the wild-type strain. We conclude that mgrA regulates virulence factors important for establishment and progression of septic arthritis and sepsis.
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| 47. |
- Jönsson, Bodil, 1959, et al.
(författare)
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Non-tuberculous mycobacteria and their surface lipids efficiently induced IL-17 production in human T cells
- 2012
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Ingår i: Microbes and Infection. - : Elsevier BV. - 1286-4579. ; 14:13, s. 1186-1195
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-17 (IL-17) is produced by a subset of CD4(+) T helper (Th) lymphocytes known as Th17 cells. In humans, IL-1 beta, enhanced by IL-6 and IL-23 is crucial for differentiation of these cells. IL-17 evokes inflammation and is involved in host defence against microorganisms, although little is known about its role in diseases caused by non-tuberculous mycobacteria. The genus Mycobacterium contains both obligate and opportunistic pathogens as well as saprophytes, and the mycobacterial cell envelope is unique in its abundance of lipids. Here we investigated IL-17 and IL-23 production in human PBMC in response to intact UV-inactivated mycobacteria and mycobacterial surface lipids from two opportunistic (Mycobacterium avium and Mycobacterium abscessus) and one generally non-pathogenic (Mycobacterium gordonae) species. Representative Gram-positive (Enterococcus faecalis, Streptococcus mitis) and Gram-negative (Escherichia coli) bacteria were included as controls. Intact mycobacteria induced production of large amounts of IL-17, while IL-17 responses to control bacteria were negligible. Purified CD4(+) T cells, but not CD4-depleted cell fractions, produced this IL-17. Isolated mycobacterial surface lipids induced IL-17, but not IL-23 production. The ability of the non-tuberculous mycobacteria to induce IL-17 production in CD4(+) T cells was the same regardless of the pathogenic potential of the particular mycobacterial species.
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| 48. |
- Jönsson, Bodil, 1959, et al.
(författare)
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The surface lipids of non-tuberculous mycobacteria suppress production of phagocyte activating cytokines in human peripheral blood mononuclear cells
- 2012
-
Ingår i: Microbes and Infection. - : Elsevier BV. - 1286-4579. ; 14:9, s. 768-777
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Tidskriftsartikel (refereegranskat)abstract
- The genus Mycobacterium includes obligate pathogens as well as opportunistic and non-pathogenic species ubiquitous in the environment. Mycobacteria have a unique cell wall abundant in lipids. Here we investigated cytokine production by human peripheral blood mononuclear cells (PBMC) in response to the opportunistic mycobacteria Mycobacterium avium and Mycobacterium abscessus, the non-pathogenic Mycobacterium gordonae and extracted surface lipids from the three species. The cytokine response elicited by mycobacteria, regardless of their pathogenic potential, differed distinctly from that induced by control Gram-positive (Enterococcus faecalis, Streptococcus mitis) and Gram-negative (Escherichia coli) bacteria. Mycobacteria induced no IL-12 and less TNF and IFN-γ compared with conventional Gram-positive bacteria. IL-10 was induced by all the mycobacteria and this production was partly responsible for the down-regulation of IL-12 and IFN-γ. The capacity of the Gram-positive bacterium E. faecalis to induce IL-12, as well as TNF and IFN-γ, in human PBMCs was strongly reduced when mycobacterial lipids were added. The mycobacterial surface lipids down-regulated the production of IL-12 and IFN-γ without eliciting IL-10 production. Our results show that mycobacteria evade triggering production of phagocyte activating cytokines (IL-12, TNF and IFN-γ) and that the mycobacterial cell wall surface lipids may play a significant role in this process.
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| 49. |
- Kahn, Fredrik, et al.
(författare)
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Platelets promote bacterial dissemination in a mouse model of streptococcal sepsis.
- 2013
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Ingår i: Microbes and Infection. - : Elsevier BV. - 1769-714X .- 1286-4579. ; 15:10-11, s. 669-676
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Tidskriftsartikel (refereegranskat)abstract
- Platelets have been reported to contribute to inflammation and inflammatory disorders. In the present study, we demonstrate that platelets contribute to the acute response to bacterial infection in a mouse model of invasive Streptococcus pyogenes infection. Thrombocytopenia occurred rapidly in infected animals and this was associated with platelet activation, formation of platelet-neutrophil complexes and neutrophil activation. In order to assess the role of platelets during infection, platelets were depleted prior to infection. Platelet-depleted animals had significantly decreased platelet-neutrophil complex formation and neutrophil activation in response to infection. Importantly, significantly fewer bacteria disseminated to the blood, lungs, and spleen of platelet-depleted animals. Platelet-depleted animals did not decrease as significantly in weight as the infected control animals. The results demonstrate a previously unappreciated role for platelets during the pathophysiological response to infection, whereby S. pyogenes bacteria bind to platelets and platelets facilitate bacterial dissemination.
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| 50. |
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