| 1. |
- Akcali, A, et al.
(författare)
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Elevated matrix metalloproteinase-8 in saliva and serum in polycystic ovary syndrome and association with gingival inflammation
- 2015
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Ingår i: Innate immunity. - : SAGE Publications. - 1753-4267 .- 1753-4259. ; 21:6, s. 619-625
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to investigate the levels of matrix metalloproteinase-8 (MMP-8) and tissue inhibitors of MMP-1 (TIMP-1) in saliva and serum samples of women with polycystic ovary syndrome (PCOS; n = 80) and matched systemically healthy controls ( n = 45), with varying degrees of gingival inflammation. Salivary levels of MMP-8 and the MMP-8/TIMP-1 ratio were significantly elevated in women with PCOS, who also exhibited more gingivitis than systemically healthy women. No major changes were observed in salivary TIMP-1 levels with regard to PCOS. Serum levels of MMP-8 and the MMP-8/TIMP-1 ratio were significantly higher in women with PCOS, irrespective of the presence of gingivitis, while there were no differences in TIMP-1 levels. A positive correlation was indicated between probing depth, bleeding on probing, plaque index and salivary or serum MMP-8 levels or MMP-8/TIMP-1 ratio in the case of PCOS, while a negative such correlation was revealed for TIMP-1 in systemically healthy women. Increased levels of MMP-8 in saliva and serum seem to be more pronounced in women with PCOS, and potentiated in the presence of gingival inflammation. Alterations in MMP/TIMP system triggered by local and systemic inflammation may be implicated in the pathogenesis of PCOS, or the deterioration of its clinical presentation.
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| 2. |
- Alfakry, H, et al.
(författare)
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Neutrophil proteolytic activation cascades: a possible mechanistic link between chronic periodontitis and coronary heart disease
- 2016
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Ingår i: Innate immunity. - : SAGE Publications. - 1753-4267 .- 1753-4259. ; 22:1, s. 85-99
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular diseases are chronic inflammatory diseases that affect a large segment of society. Coronary heart disease (CHD), the most common cardiovascular disease, progresses over several years and affects millions of people worldwide. Chronic infections may contribute to the systemic inflammation and enhance the risk for CHD. Periodontitis is one of the most common chronic infections that affects up to 50% of the adult population. Under inflammatory conditions the activation of endogenous degradation pathways mediated by immune responses leads to the release of destructive cellular molecules from both resident and immigrant cells. Matrix metalloproteinases (MMPs) and their regulators can activate each other and play an important role in immune response via degrading extracellular matrix components and modulating cytokines and chemokines. The action of MMPs is required for immigrant cell recruitment at the site of inflammation. Stimulated neutrophils represent the major pathogen-fighting immune cells that upregulate expression of several proteinases and oxidative enzymes, which can degrade extracellular matrix components (e.g. MMP-8, MMP-9 and neutrophil elastase). The activity of MMPs is regulated by endogenous inhibitors and/or candidate MMPs (e.g. MMP-7). The balance between MMPs and their inhibitors is thought to mirror the proteolytic burden. Thus, neutrophil-derived biomarkers, including myeloperoxidase, may activate proteolytic destructive cascades that are involved in subsequent immune-pathological events associated with both periodontitis and CHD. Here, we review the existing studies on the contribution of MMPs and their regulators to the infection-related pathology. Also, we discuss the possible proteolytic involvement and role of neutrophil-derived enzymes as an etiological link between chronic periodontitis and CHD.
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| 3. |
- Andersson, Märta, et al.
(författare)
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Mycobacterium bovis bacilli Calmette-Guerin regulates leukocyte recruitment by modulating alveolar inflammatory responses.
- 2012
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Ingår i: Innate Immunity. - : SAGE Publications. - 1753-4267 .- 1753-4259. ; 18, s. 531-540
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Tidskriftsartikel (refereegranskat)abstract
- Leukocyte migration into the epithelial compartment is an important feature in the active phase of mycobacterial infections. In this study, we used the Transwell model to investigate the mechanisms behind mycobacteria-induced leukocyte recruitment and investigated the role of TLR2 and TLR4 in this process. Infection of epithelial cells resulted in significantly increased secretion of the neutrophil chemotactic CXCL8 and IL-6, but no secretion of monocyte chemotactic CCL2 or TNF-α was observed. In contrast to epithelial response, mycobacteria-infected neutrophils and monocytes secreted all these cytokines. Corresponding with epithelial cytokine response, mycobacterial infection of the epithelial cells increased neutrophil diapedesis, but decreased monocyte recruitment. However, monocyte recruitment towards mycobacteria infected epithelial cells significantly increased following addition of neutrophil pre-conditioned medium. Mycobacterial infection also increases alveolar epithelial expression of TLR2, but not TLR4, as analyzed by flow cytometry, Western blotting and visualized by confocal microscopy. Blocking of TLR2 inhibited neutrophil recruitment and cytokine secretion, while blocking of TLR4 had a lesser effect. To summarize, we found that primary alveolar epithelial cells produced a selective TLR2-dependent cytokine secretion upon mycobacterial infection. Furthermore, we found that cooperation between cells of the innate immunity is required in mounting proper antimicrobial defence.
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| 4. |
- Blidberg, K, et al.
(författare)
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Chemokine release by neutrophils in chronic obstructive pulmonary disease
- 2012
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Ingår i: Innate immunity. - : SAGE Publications. - 1753-4267 .- 1753-4259. ; 18:3, s. 503-510
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophils are among the first cells to arrive at the site of injury. Chemokines secreted by neutrophils affect the migration of both neutrophils and other inflammatory cells, such as monocytes. It has been reported that LPS-induced release of IL-8 (CXCL-8) by neutrophils is amplified by neutrophil-derived TNF-α. We hypothesize that chemokine release by neutrophils is altered in chronic obstructive pulmonary disease (COPD) compared with healthy controls and that TNF-α may be involved in this alteration. Peripheral blood neutrophils isolated from smokers with COPD ( n = 12), smokers without COPD ( n = 12) and healthy, non-smokers ( n = 12) were stimulated with LPS, TNF-α or organic dust. Anti-TNF-α Ab (infliximab) was used to study the effect of neutrophil-derived TNF-α. Release of CXCL-8, macrophage inflammatory protein-1 α (MIP-1α, CCL-3), monocyte chemotactic protein-1 (MCP-1, CCL-2) and TNF-α was measured. Neutrophils spontaneously released CXCL-8, CCL-2 and CCL-3. Inhibition of TNF-α reduced the spontaneous release of CXCL-8 and CCL-3. Stimulation with LPS and organic dust increased the release of CXCL-8 and CCL-3 (but not CCL-2) which was reduced by inhibition of TNF-α. In the COPD group, inhibition of TNF-α failed to inhibit the release of LPS-induced CXCL-8. The role of neutrophils as cytokine and chemokine producers was confirmed. Neutrophil-derived TNF-α contributed to the release of chemokines after stimulation with LPS and organic dust, as the response was inhibited by infliximab. In the COPD group, infliximab did not significantly inhibit the release of CXCL-8, suggesting that the role of TNF-α is altered in COPD.
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| 5. |
- Hashemian, Sanaz, et al.
(författare)
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TLR4 receptor expression and function in F11 dorsal root ganglion x neuroblastoma hybrid cells
- 2017
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Ingår i: Innate Immunity. - : SAGE Publications. - 1753-4259 .- 1753-4267. ; 23:8, s. 687-696
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Tidskriftsartikel (refereegranskat)abstract
- TLR4 respond to bacterial LPS to produce inflammatory cytokines. TLR4 are expressed in dorsal root ganglia and play a role in pain. F11 dorsal root ganglia x mouse neuroblastoma cells possess many of the properties seen in nociceptive dorsal root ganglia neuronal cells. Here, we investigated the effect of 2h and 6h treatment with LPS upon the expression of inflammatory proteins in undifferentiated and differentiated F11 cells. The cells expressed mRNA for TRL4 (mouse, not rat) and proteins involved in TLR4 signaling. TLR4 expression was confirmed using immunohistochemistry. LPS produced modest increases in mouse and rat IL-6 and in mouse cyclooxygenase-2 levels in undifferentiated cells, but did not significantly affect mouse TNF- expression. This contrasts with the robust effects of LPS upon cyclooxygenase-2 expression in cultured dorsal root ganglia neurons. F11 cells expressed the endocannabinoid metabolizing enzymes fatty acid amide hydrolase and N-acylethanolamine acid amidase (both murine), which were functionally active. These data suggest that F11 cells are not a useful model for the study of LPS-mediated effects but may be useful for the study of endocannabinoid catabolism.
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| 6. |
- Kallio, KAE, et al.
(författare)
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Lipopolysaccharide associates with pro-atherogenic lipoproteins in periodontitis patients
- 2008
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Ingår i: Innate immunity. - : SAGE Publications. - 1753-4259 .- 1753-4267. ; 14:4, s. 247-253
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Periodontitis patients are known to suffer from endotoxemia, which may be among the major risk factors for atherosclerosis. In health, lipopolysaccharide (LPS) is mainly carried with high density lipoprotein (HDL) particles. Shift of LPS toward lipoproteins with lower densities may result in less effective endotoxin scavenging. Our aim was to determine plasma LPS activity and lipoprotein-distribution before and after treatment in periodontitis patients. Patients and Methods: Very low and intermediate density (VLDL-IDL), low density (LDL), HDL 2, HDL3, and lipoprotein-deficient plasma (LPDP) were isolated by sequential ultracentrifugation. Patients included 34 subjects aged 53.5 ± 8.3 years, before and 6 months after periodontal treatment. Results: The mean LPS distribution decreased among lipoprotein classes as follows: VLDL-IDL 41.3 ± 12.1%, LPDP 25.0 ± 7.0%, HDL3 13.1 ± 5.2%, LDL 11.5 ± 3.7%, and HDL2 9.2 ± 2.8%. Plasma and VLDL-IDL-associated LPS correlated positively, and LDL- and HDL-associated LPS negatively with clinical periodontal parameters and plasma cytokine concentrations. Mean plasma LPS activity increased after periodontal treatment from 44.0 ± 17.0 to 55.7 ± 24.2 EU/ml ( P = 0.006). No significant changes were found in LPS lipoprotein distribution and lipoprotein compositions after the treatment. Conclusions: Endotoxemia increases with severity of periodontitis. In periodontitis, LPS associates preferentially with the pro-atherogenic VLDL-IDL fraction. Periodontal treatment has only minor effects on plasma LPS activity or distribution, which reflects persistence of the disease.
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| 7. |
- Lipcsey, Miklós, et al.
(författare)
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The time course of calprotectin liberation from human neutrophil granulocytes after Escherichia coli and endotoxin challenge
- 2019
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Ingår i: Innate Immunity. - : SAGE Publications. - 1753-4259 .- 1753-4267. ; 25:6, s. 369-373
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Tidskriftsartikel (refereegranskat)abstract
- Plasma calprotectin has previously been reported as a biomarker for sepsis. The aim of the present study was to elucidate the kinetics of calprotectin release from neutrophils exposed to Escherichia coli and endotoxin. Whole blood samples were exposed to E. coli bacteria or endotoxin in vitro. Blood samples were collected after 0, 1, 2, 3 and 4 h and plasma calprotectin was analysed by particle enhanced turbidimetric immunoassay while TNF-α, IL-6, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were analyzed by ELISA. When neutrophils were exposed to either E. coli or endotoxin, calprotectin levels began to increase within a couple of hours after the challenge. Calprotectin increases early in response to bacterial challenge. Given the logistic advantages of the calprotectin analysis, this may be of interest for early diagnosis of bacterial infections.
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| 8. |
- Liukkonen, J, et al.
(författare)
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Salivary biomarkers in association with periodontal parameters and the periodontitis risk haplotype
- 2018
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Ingår i: Innate immunity. - : SAGE Publications. - 1753-4267 .- 1753-4259. ; 24:7, s. 439-447
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Tidskriftsartikel (refereegranskat)abstract
- Genetic factors play a role in periodontitis. Here we examined whether the risk haplotype of MHC class III region BAT1-NFKBIL1-LTA and lymphotoxin-α polymorphisms associate with salivary biomarkers of periodontal disease. A total of 455 individuals with detailed clinical and radiographic periodontal health data were included in the study. A 610 K genotyping chip and a Sequenom platform were used in genotyping analyses. Phospholipid transfer protein activity, concentrations of lymphotoxin-α, IL-8 and myeloperoxidase, and a cumulative risk score (combining Porphyromonas gingivalis, IL-1β and matrix metalloproteinase-8) were examined in saliva samples. Elevated IL-8 and myeloperoxidase concentrations and cumulative risk scores associated with advanced tooth loss, deepened periodontal pockets and signs of periodontal inflammation. In multiple logistic regression models adjusted for periodontal parameters and risk factors, myeloperoxidase concentration (odds ratio (OR); 1.37, P = 0.007) associated with increased odds for having the risk haplotype and lymphotoxin-α concentration with its genetic variants rs2857708, rs2009658 and rs2844482. In conclusion, salivary levels of IL-8, myeloperoxidase and cumulative risk scores associate with periodontal inflammation and tissue destruction, while those of myeloperoxidase and lymphotoxin-α associate with genetic factors as well.
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| 9. |
- Nguyen, D. N., et al.
(författare)
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Elevated levels of circulating cell-free DNA and neutrophil proteins are associated with neonatal sepsis and necrotizing enterocolitis in immature mice, pigs and infants
- 2017
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Ingår i: Innate Immunity. - : SAGE Publications. - 1753-4259 .- 1753-4267. ; 23:6, s. 524-536
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Tidskriftsartikel (refereegranskat)abstract
- Preterm infants are highly susceptible to late-onset sepsis (LOS) and necrotizing enterocolitis (NEC), but disease pathogenesis and specific diagnostic markers are lacking. Circulating cell-free DNA (cfDNA) and immune cell-derived proteins are involved in multiple immune diseases in adults but have not been investigated in preterm neonates. We explored the relation of circulating neutrophil-associated proteins and cfDNA to LOS and/or NEC. Using a clinically relevant preterm pig model of spontaneous LOS and NEC development, we investigated neutrophil-associated proteins and cfDNA in plasma, together with cytokines in gut tissues. The changes in cfDNA levels were further studied in preterm pigs and neonatal mice with induced sepsis, and in preterm infants with or without LOS and/or NEC. Fifteen of 114 preterm pigs spontaneously developed both LOS and NEC, and they showed increased intestinal levels of IL-6 and IL-1 and plasma levels of cfDNA, neutrophil-associated proteins, and proteins involved in platelet-neutrophil interaction during systemic inflammation. The abundance of neutrophil-associated proteins highly correlated with cfDNA levels. Further, Staphylococcus epidermidis challenge of neonatal mice and preterm pigs increased plasma cfDNA levels and bacterial accumulation in the spleen. In infants, plasma cfDNA levels were elevated at LOS diagnosis and 1-6d before NEC. In conclusion, elevated levels of plasma cfDNA and neutrophil proteins are associated with LOS and NEC diagnosis.
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| 10. |
- Nousiainen, L, et al.
(författare)
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Human kinome analysis reveals novel kinases contributing to virus infection and retinoic-acid inducible gene I-induced type I and type III IFN gene expression
- 2013
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Ingår i: Innate immunity. - : SAGE Publications. - 1753-4267 .- 1753-4259. ; 19:5, s. 516-530
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Tidskriftsartikel (refereegranskat)abstract
- Activation of host innate antiviral responses are mediated by retinoic-acid inducible gene I ( RIG-I)-like receptors, RIG-I and melanoma differentiation-associated gene 5, and TLRs 3, 7, 8 and 9, recognising different types of viral nucleic acids. The major components of the RIG-I- and TLR pathways have putatively been identified, but previously unrecognised kinases may contribute to virus infection-induced activation of the IFN response. Here, we screened a human kinase cDNA library, termed the kinome, using an IFN-λ1 promoter-driven luciferase reporter assay in HEK293 cells during Sendai virus infection. Of the 568 kinases analysed, nearly 50 enhanced IFN-λ1 gene expression at least twofold in response to Sendai virus infection. The best activators were FYN ( FYN oncogene related to SRC, FGR, YES), serine/threonine kinase 24, activin A receptor type 1 and SRPK1 (SFRS protein kinase 1). These kinases enhanced RIG-I-dependent IFN-λ1 promoter activation via IFN-stimulated response and NF-κB elements, as confirmed using mutant IFN-λ1 promoter constructs. FYN and SRPK1 enhanced IFN-λ1 and CXCL10 protein production via the RIG-I pathway, and stimulated RIG-I and MyD88-dependent phosphorylation of IRF3 and IRF7 transcription factors, respectively. We conclude that several previously unrecognised kinases, particularly FYN and SRPK1, positively regulate IFN-λ1 and similarly regulated cytokine and chemokine genes during viral infection.
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| 11. |
- Nylen, F, et al.
(författare)
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Boosting innate immunity: development and validation of a cell-based screening assay to identify LL-37 inducers
- 2014
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Ingår i: Innate immunity. - : SAGE Publications. - 1753-4267 .- 1753-4259. ; 20:4, s. 364-376
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Tidskriftsartikel (refereegranskat)abstract
- Innate immunity, the front line of our defence against pathogens, relies, to a great extent, on the production of antimicrobial peptides (AMPs). These peptides exhibit antimicrobial activity and immunomodulatory properties. In humans, AMPs include the defensins (α- and β-families) and the cathelicidin, LL-37. Bacterial resistance against antibiotics is a growing concern, and novel antimicrobial strategies are needed urgently. Hence, the concept of strengthening immune defences against infectious microbes by inducing AMP expression may represent novel or complementary pharmaceutical interventions in the treatment or prevention of infections. We have developed and validated a robust cell-based reporter assay for LL-37 expression, which serves as a marker for a healthy epithelial barrier. This reporter assay can be a powerful tool for high-throughput screenings. We first employed our assay to screen a panel of histone deacetylase inhibitors and derivatives, and then the Prestwick Chemical Library of Food and Drug Administration-approved compounds. After hit confirmation and independent validation in the parental cell line we identified five novel inducers of LL-37. This reporter assay will help to identify novel drug candidates for the treatment and prevention of infections. Importantly, the pattern of hits obtained may suggest cellular pathways and key mediators involved in the regulation of AMP expression.
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| 12. |
- Olsson, Lars E, et al.
(författare)
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1H and hyperpolarized 3He magnetic resonance imaging clearly detect the preventative effect of a glucocorticoid on endotoxin-induced pulmonary inflammation in vivo.
- 2010
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Ingår i: Innate immunity. - : SAGE Publications. - 1753-4267 .- 1753-4259. ; :Feb 3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Proton ((1)H) magnetic resonance imaging (MRI) can be utilized to quantify pulmonary edema in endotoxin-induced pulmonary inflammation and hyperpolarized (HP) (3)He MRI can assess pulmonary ventilation. Neither of the methods has been applied to assess the impact of a drug on endotoxin-induced pulmonary inflammation in vivo. The aim of the current study was to evaluate the capability of (1)H and HP (3)He MRI to assess the effects of a glucocorticoid on endotoxin-induced pulmonary inflammation in vivo.Materials and Methods: Mice were exposed to an aerosol of either saline or endotoxin (5 mg/ml) for 10 min. Half of the endotoxin-exposed mice were pretreated with a glucocorticoid (budesonide 3 mg/kg; 2 times/day) and the other half with vehicle p.o. The first budesonide treatment was administered 1 h prior to the aerosol inhalation. Forty-eight hours after the aerosol exposure, the mice were anaesthetized for subsequent imaging. Hyperpolarized (3)He was administered and axial MR images of the lungs obtained. Matching (1)H MR images were then acquired. The mice were sacrificed and broncho-alveolar lavage (BAL) samples were harvested to determine total and cell differential counts.Results: The lesion volume on both (1)H and (3)He MRI, were markedly increased by endotoxin exposure (P < 0.001). Budesonide strongly reduced lesion volume (P < 0.001). The BAL cell count correlated strongly with both (3)He (P < 0.001; r = 0.96) and (1)H lesion volumes (P < 0.001; r = 0.97).Conclusions: Hyperpolarized (3)He MRI and (1)H MRI clearly visualized the preventative effect of budesonide on the impact of endotoxin on pulmonary ventilation and edema, respectively. The fact that ventilation defects on (3)He MRI corresponded to findings from conventional (1)H MRI, as well as to counts of BAL inflammatory cells suggests that these imaging techniques constitute promising tools for non-invasive monitoring of pulmonary inflammation in vivo.
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| 13. |
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| 14. |
- Otterbeck, Alexander, et al.
(författare)
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Intravenous anti-P. aeruginosa IgY-antibodies do not decrease pulmonary bacterial concentrations in a porcine model of ventilator-associated pneumonia
- 2022
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Ingår i: Innate Immunity. - : Sage Publications. - 1753-4259 .- 1753-4267. ; 28:7-8, s. 224-234
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Tidskriftsartikel (refereegranskat)abstract
- Ventilator associated pneumonia (VAP) caused by P. aeruginosa is a cause of morbidity and mortality in critically ill patients. The spread of pathogens with anti-microbial resistance mandates the investigation of novel therapies. Specific polyclonal anti-P. aeruginosa IgY-antibodies (Pa-IgY) might be effective for VAP caused by P. aeruginosa. The objective of this study was to investigate if intravenous Pa-IgY decreases the lower airway concentration of P. aeruginosa in VAP. We used a double blind randomized placebo controlled porcine model of VAP caused by P. aeruginosa. Eighteen pigs were randomized to either receive intravenous Pa-IgY or placebo. Repeated registration of physiological parameters and sampling was performed for 27 h. Concentration of P. aeruginosa in BAL-cultures was similar in both groups with 104.97 ± 102.09 CFU/mL in the intervention group vs 104.37 ± 102.62 CFU/mL in the control group at the end of the experiment. The intervention group had higher heart rate, cardiac index, oxygen delivery and arterial oxygen tension/fraction of inspired oxygen-ratio, but lower plasma lactate and blood hemoglobin levels than the control group. In summary, in an anesthetized and mechanically ventilated porcine model of VAP, Pa-IgY at the dose used did not decrease concentrations of P. aeruginosa in the lower airways.
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| 15. |
- Sahlander, K, et al.
(författare)
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Altered innate immune response in farmers and smokers
- 2010
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Ingår i: Innate immunity. - : SAGE Publications. - 1753-4267 .- 1753-4259. ; 16:1, s. 27-38
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Tidskriftsartikel (refereegranskat)abstract
- Pig farmers and cigarette smokers are continuously exposed to pathogen-associated molecular patterns (PAMPs) have an increased prevalence of respiratory disorders, such as chronic bronchitis and chronic obstructive pulmonary decease (COPD). We hypothesized that markers of innate immunity, T-helper (Th) cell cytokine profile and acute responses to pro-inflammatory stimuli differ between smokers and farmers, who are exposed to organic material on a daily basis and healthy non-exposed subjects. Eleven non-smoking pig farmers, 12 non-farming smokers and 12 controls underwent bronchial lipopolysaccharide (LPS) challenge and exposure in a pig barn during 3 h on separate days. Toll-like receptor 2 (TLR2), TLR4 and CD14 on blood monocytes and neutrophils and intracellular cytokine profile of Th cells were assessed before and 7 h after exposures. The same outcomes were analysed on peripheral blood and purified neutrophils from farmers and controls after stimulation ex vivo with dust from a pig barn and LPS. Circulating neutrophils and IL-13 and IL-4 producing Th cells were increased in smokers and farmers and TLR2 expression on blood monocytes was decreased in farmers compared with controls and smokers. After in vivo exposure, altered TLR expression was only observed in controls and the ex vivo stimulations showed an attenuated response in farmers compared to the control group. The inflammatory systemic response to pro-inflammatory stimuli is altered in farmers and smokers probably because of adaptive mechanisms arising from chronic exposure to organic material. This increased proportion of Th2 cells and reduced TLR2 expression may have health-related implications and may be related to the increased prevalence of respiratory disorders observed in these groups.
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| 16. |
- Schweda, Elke K. H., et al.
(författare)
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Profiling structural elements of short-chain lipopolysaccharide of non-typeable Haemophilus influenzae
- 2008
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Ingår i: Innate Immunity. - : SAGE Publications. - 1753-4259 .- 1753-4267. ; 14:4, s. 199-211
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Tidskriftsartikel (refereegranskat)abstract
- Lipopolysaccharide (LPS) is a major Virulence determinant of the human bacterial pathogen Hoemophilus influenzae. A characteristic feature of H. influenzae LPS is the extensive intra- and inter-strain heterogeneity of glycoform structure which is key to the role of the molecule in both commensal and disease-causing behaviour of the bacterium. The chemical composition of non-typeable Haemophilus influenzae (NTHi) LPS is hi-lily diverse. It contains a number of different monosaccharides (Neu5Ac, L-glycero-D-manno heptose, D-glycero-D-manno heptose, Kdo, D-Glc, D-Gal, D-GlcNAc, D-GaINAc) and non-carbohydrate substituents. Prominent non-carbohydrate components are O-acetyl groups, glycine and phosphates. We now know that sialic acid (N-acetylneuraminic acid or Neu5Ac) and certain oligosaccharide extensions are important in the pathogenesis of NTHi: however, the biological implications for many of the various features are Still unknown. Electrospray ionization mass spectrometry ill combination with separation techniques like CE and HPLC is an indispensable tool in profiling glycoform populations ill heterogeneous LPS samples. Mass Spectrometry is characterized by its extreme sensitivity. Trace amounts of glycoforms expressing important Virulence determinants can be detected and characterized on minute amounts of material. The present review focuses oil LPS structures and mass spectrometric methods which enable us to profile these in complex mixtures.
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| 17. |
- Sejersen, Kristina, et al.
(författare)
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Early kinetics of calprotectin in plasma following inguinal hernia surgery
- 2022
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Ingår i: Innate Immunity. - : Sage Publications. - 1753-4259 .- 1753-4267. ; 28:1, s. 49-54
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Tidskriftsartikel (refereegranskat)abstract
- Calprotectin is one of the most abundant proteins of neutrophil granulocytes. It is released upon neutrophil activation and is considered a sensitive and clinically useful marker for neutrophil-mediated inflammation, including bacterial infections. However, early kinetics of calprotectin activation following inflammatory activation has hitherto been unknown. The aim of the present study was to determine the early phase of the kinetics of calprotectin, in comparison with the inflammatory markers CRP, IL-6, TNF-α, and procalcitonin, in plasma following a standardized temporary mild inflammatory response, using uncomplicated inguinal hernia surgery as a model. The study cohort consisted of 17 adult patients (15 male and 2 female) undergoing elective surgery for hernia. Values of calprotectin increased significantly at 2 h following surgery, and continued to increase to reach the highest level at 24-36 h after surgery, values still not exceeding upper normal reference level. This contrasts to IL-6 and CRP, for which an elevation was found first later, 4 h and 24-36 h post-surgery, respectively, for IL-6, and CRP. No significant increase was seen for TNF-α, or procalcitonin. The data demonstrate a very rapid and significant but modest increase in calprotectin following induction of mild inflammation, supporting that calprotectin can be useful for early detection of inflammatory response.
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| 18. |
- Silverpil, Elin, 1978, et al.
(författare)
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Negative feedback on IL-23 exerted by IL-17A during pulmonary inflammation
- 2013
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Ingår i: Innate Immunity. - : SAGE Publications. - 1753-4259 .- 1753-4267. ; 19:5, s. 479-492
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Tidskriftsartikel (refereegranskat)abstract
- It is now established that IL-17 has a broad pro-inflammatory potential in mammalian host defense, in inflammatory disease and in autoimmunity, whereas little is known about its anti-inflammatory potential and inhibitory feedback mechanisms. Here, we examined whether IL-17A can inhibit the extracellular release of IL-23 protein, the upstream regulator of IL-17A producing lymphocyte subsets, that is released from macrophages during pulmonary inflammation. We characterized the effect of IL-17A on IL-23 release in several models of pulmonary inflammation, evaluated the presence of IL-17 receptor A (RA) and C (RC) on human alveolar macrophages and assessed the role of the Rho family GTPase Rac1 as a mediator of the effect of IL-17A on the release of IL-23 protein. In a model of sepsis-induced pneumonia, intravenous exposure to Staphylococcus aureus caused higher IL-23 protein concentrations in cell-free bronchoalveolar lavage (BAL) samples from IL-17A knockout (KO) mice, compared with wild type (WT) control mice. In a model of Gram-negative airway infection, pre-treatment with a neutralizing anti-IL-17A Ab and subsequent intranasal (i.n.) exposure to LPS caused higher IL-23 and IL-17A protein concentrations in BAL samples compared with mice exposed to LPS, but pre-treated with an isotype control Ab. Moreover, i.n. exposure with IL-17A protein per se decreased IL- 23 protein concentrations in BAL samples. We detected IL-17RA and IL-17RC on human alveolar macrophages, and found that invitro stimulation of these cells with IL-17A protein, after exposure to LPS, decreased IL-23 protein in conditioned medium, but not IL-23 p19 or p40 mRNA. This study indicates that IL-17A can partially inhibit the release of IL-23 protein during pulmonary inflammation, presumably by stimulating the here demonstrated receptor units IL-17RA and IL-17RC on alveolar macrophages. Hypothetically, the demonstrated mechanism may serve as negative feedback to protect from excessive IL-17A signaling and to control antibacterial host defense once it is activated.
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| 19. |
- Troseid, M, et al.
(författare)
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Circulating levels of HMGB1 are correlated strongly with MD2 in HIV-infection: possible implication for TLR4-signalling and chronic immune activation
- 2013
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Ingår i: Innate immunity. - : SAGE Publications. - 1753-4267 .- 1753-4259. ; 19:3, s. 290-297
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Tidskriftsartikel (refereegranskat)abstract
- Progressive HIV infection is characterized by profound enterocyte damage, microbial translocation and chronic immune activation. We aimed to test whether High Mobility Group Box protein 1(HMGB1), a marker of cell death, alone, or in combination with LPS, might contribute to HIV-associated immune activation and progression. Altogether, 29 untreated HIV-infected individuals, 25 inflammatory bowel disease (IBD) patients and 30 controls were included. HIV-infected patients had lower plasma LPS levels than IBD patients, but higher levels of soluble CD14 and Myeloid Differentiation (MD) 2, which interacts with TLR4 to initiate LPS-signalling. Furthermore, plasma levels of HMGB1 and MD2 were correlated directly within the HIV-infected cohort (r = 0.89, P < 0.001) and the IBD-cohort (r = 0.85, P < 0.001), implying HMGB1 signalling through the MD2/TLR4-pathway. HMGB1 and LPS, although not inter-correlated, were both moderately (r = 0.4) correlated with CD38 density on CD8+ T cells in HIV progressors. The highest levels of CD38 density and MD2 were found in progressors with plasma levels of both LPS and HMGB1 above the fiftieth percentile. Our results could imply that, in some patients, immune activation is triggered by microbial translocation, in some by cell death and in some by HMGB1 in complex with bacterial products through activation of the MD2/TLR4-pathway.
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| 20. |
- Turunen, S. Pauliina, et al.
(författare)
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Immunization with malondialdehyde-modified low-density lipoprotein (LDL) reduces atherosclerosis in LDL receptor-deficient mice challenged with Porphyromonas gingivalis
- 2015
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Ingår i: Innate Immunity. - : SAGE Publications. - 1753-4259 .- 1753-4267. ; 21:4, s. 370-85
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Tidskriftsartikel (refereegranskat)abstract
- Periodontal infections increase the risk of atherosclerotic vascular disease via partly unresolved mechanisms. Of the natural IgM Abs that recognize molecular mimicry on bacterial epitopes and modified lipid and protein structures, IgM directed against oxidized low-density lipoprotein (LDL) is associated with atheroprotective properties. Here, the effect of natural immune responses to malondialdehyde-modified LDL (MDA-LDL) in conferring protection against atherosclerosis, which was accelerated by the major periodontopathogen Porphyromonas gingivalis, was investigated. LDL receptor-deficient (LDLR(-/-)) mice were immunized with mouse MDA-LDL without adjuvant before topical application challenge with live P. gingivalis. Atherosclerosis was analyzed after a high-fat diet, and plasma IgG and IgM Ab levels were measured throughout the study, and the secretion of IL-5, IL-10 and IFN-γ in splenocytes stimulated with MDA-LDL was determined. LDLR(-/-) mice immunized with MDA-LDL had elevated IgM and IgG levels to MDA-LDL compared with saline-treated controls. MDA-LDL immunization diminished aortic lipid depositions after challenge with P. gingivalis compared with mice receiving only P. gingivalis challenge. Immunization of LDLR(-/-) mice with homologous MDA-LDL stimulated the production of IL-5, implicating general activation of B-1 cells. Immune responses to MDA-LDL protected from the P. gingivalis-accelerated atherosclerosis. Thus, the linkage between bacterial infectious burden and atherogenesis is suggested to be modulated via natural IgM directed against cross-reactive epitopes on bacteria and modified LDL.
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| 21. |
- Yong, Yean K., et al.
(författare)
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Decrease of CD69 levels on TCR V7.2(+)CD4(+) innate-like lymphocytes is associated with impaired cytotoxic functions in chronic hepatitis B virus-infected patients
- 2017
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Ingår i: Innate Immunity. - : SAGE PUBLICATIONS LTD. - 1753-4259 .- 1753-4267. ; 23:5, s. 459-467
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Tidskriftsartikel (refereegranskat)abstract
- Hepatitis B virus (HBV) infection is a major cause of chronic liver disease that may progress to liver cirrhosis and hepatocellular carcinoma. Host immune responses represent the key determinants of HBV clearance or persistence. Here, we investigated the role of the early activation marker, CD69 and effector cytokines, granzyme B (GrB) and IFN- in the exhaustion of innate-like TCR V7.2(+)CD4(+)T cells, in 15 individuals with chronic HBV (CHB) infection where six were HBV DNA(+) and nine were HBV DNA(-). The percentage of cytokine-producing T cells and MAIT cells were significantly perturbed in HBV patients relative to healthy controls (HCs). The intracellular expression of GrB and IFN- was significantly reduced in MAIT cells derived from HBV-infected patients as compared to HCs, and the levels correlated with the percentage and levels [mean fluorescence intensity (MFI)] of CD69 expression. The total expression of CD69 (iMFI) was lower in CHB patients as compared to HCs. The frequency of CD69(+) cells correlated with the levels of cytokine expression (MFI), particularly in CHB patients as compared to HCs. In summary, the polyfunctionality of peripheral T cells was significantly reduced among CHB patients, especially in the TCR V7.2(+)CD4(+)T cells, and the levels of cytokine expression correlated with functional cytokine levels.
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| 22. |
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| 23. |
- Lindgren, Åsa, 1979, et al.
(författare)
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Interferon-gamma secretion is induced in IL-12 stimulated human NK cells by recognition of Helicobacter pylori or TLR2 ligands
- 2011
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Ingår i: Innate Immunity. - 1753-4267. ; 17:2, s. 191-203
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori induce a chronic inflammation in the human gastric mucosa characterized by increased production of interferon-gamma (IFN-γ). The presence of natural killer (NK) cells in the human gastric mucosa and the ability of NK cells to produce IFN-γ suggest an important role of NK cells in the immune response directed towards H. pylori infection. Since NK cells previously have been shown to respond to bacterial components with IFN-γ production, we investigated the mechanisms for the recognition of H. pylori. We found that inhibition of MyD88 homodimerization resulted in decreased production of IFN-γ and that inhibition of the p38 MAPK decreased the production as well as the secretion of IFN-γ. Further studies indicated an involvement of Toll-like receptors (TLRs), in particular TLR2. Finally, we showed that the H. pylori specific membrane bound lipoprotein HpaA induced IFN-γ production from NK cells through recognition by TLR2. In conclusion, we suggest an involvement of TLR2 in the recognition of H. pylori by human NK cells and that HpaA is a TLR2 ligand important for recognition.
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