| 1. |
- Godaly, Gabriela, et al.
(författare)
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Mycobacterium bovis bacille Calmette Guerin infection of human neutrophils induces CXCL8 secretion by MyD88-dependent TLR2 and TLR4 activation
- 2005
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Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 7:4, s. 591-601
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the potential role of neutrophils in initiation of immune responses to mycobacteria, we have characterized the response of human neutrophils to infection with Mycobacterium bovis bacille Calmette Guerin, the BCG vaccine. BCG induced transcription and secretion of the chemokine CXCL8, by signalling through Toll-like receptors TLR2 and TLR4, in conjunction with the adaptor protein myeloid differentiation factor 88 (MyD88). Blocking of responses with antibodies revealed a difference in the kinetics of signalling through the different TLRs. Anti-TLR2 antibody blocked the early phase of CXCL8 and MyD88 induction. Anti-TLR4 antibody blocked the late phase of induction occurring 2 h after infection. The existence of a TLR/MyD88 pathway for recognition and response to mycobacterial ligands provides neutrophils with the ability to drive the recruitment and activation of inflammatory cells during the early phase of mycobacterial infection and immunization.
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| 2. |
- Paz, Irit, et al.
(författare)
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Galectin-3, a marker for vacuole lysis by invasive pathogens
- 2010
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Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 12:4, s. 530-544
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Tidskriftsartikel (refereegranskat)abstract
- P>Shigella bacteria invade macrophages and epithelial cells and following internalization lyse the phagosome and escape to the cytoplasm. Galectin-3, an abundant protein in macrophages and epithelial cells, belongs to a family of beta-galactoside-binding proteins, the galectins, with many proposed functions in immune response, development, differentiation, cancer and infection. Galectins are synthesized as cytosolic proteins and following non-classical secretion bind extracellular beta-galactosides. Here we analysed the localization of galectin-3 following entry of Shigella into the cytosol and detected a striking phenomenon. Very shortly after bacterial invasion, intracellular galectin-3 accumulated in structures in vicinity to internalized bacteria. By using immuno-electron microscopy analysis we identified galectin-3 in membranes localized in the phagosome and in tubules and vesicles that derive from the endocytic pathway. We also demonstrated that the binding of galectin-3 to host N-acetyllactosamine-containing glycans, was required for forming the structures. Accumulation of the structures was a type three secretion system-dependent process. More specifically, existence of structures was strictly dependent upon lysis of the phagocytic vacuole and could be shown also by Gram-positive Listeria and Salmonella sifA mutant. We suggest that galectin-3-containing structures may serve as a potential novel tool to spot vacuole lysis.
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| 3. |
- Påhlman, Lisa, et al.
(författare)
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Soluble M1 protein of Streptococcus pyogenes triggers potent T cell activation.
- 2008
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Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 10:2, s. 404-414
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes of the M1 serotype is commonly associated with large outbreaks of invasive streptococcal infections and development of streptococcal toxic shock syndrome (STSS). The pathogenesis behind these infections is believed to involve bacterial superantigens that induce potent inflammatory responses, but the reason why strains of the M1 serotype are over-represented in STSS is still not understood. In the present investigation, we show that a highly purified soluble form of the M1 protein from S. pyogenes, which lacks the membrane-spanning region, is a potent inducer of T cell proliferation and release of Th1 type cytokines. M1 protein-evoked T cell proliferation was HLA class II-dependent but not MHC-restricted, did not require intracellular processing and was Vβ-restricted. Extensive mass spectrometry studies indicated that there were no other detectable proteins in the preparation. Taken together, our data demonstrate that soluble M1 protein is a novel streptococcal superantigen, which likely contributes to the excessive T cell activation and hyperinflammatory response seen in severe invasive streptococcal infections.
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| 4. |
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| 5. |
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| 6. |
- Wullt, Björn, et al.
(författare)
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P-fimbriae trigger mucosal responses to Escherichia coli in the human urinary tract
- 2001
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Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 3:4, s. 255-264
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Tidskriftsartikel (refereegranskat)abstract
- Uropathogenic Escherichia coli elicit a host response that determines the severity of urinary tract infection (UTI). Specific adherence mechanisms allow the bacteria to initiate this process by targeting epithelial cells in the urinary tract mucosa. Epidemiological studies show a strong association of P-fimbriae with disease severity, suggesting that adherence mediated by these organelles has a direct effect on mucosal inflammation in vivo. The present study examined the ability of P-fimbriae to induce inflammation in the human urinary tract. Patients were subjected to intravesical inoculation with a non-fimbriated E. coli strain or transformants of this strain expressing P-fimbriae. The inflammatory response was analysed as a function of P-fimbrial expression. The P-fimbriated transformants invariably caused higher interleukin (IL)-8, IL-6 and neutrophil responses in the urinary tract than the ABU strain. Furthermore, loss of P-fimbrial expression in vivo was accompanied by a return to background levels of neutrophils, IL-6 and IL-8 in individual patients. The results demonstrate that the pap sequences confer on a non-fimbriated, avirulent strain the ability to induce a host response in the human urinary tract. P-fimbriae thus fulfil the 'molecular Koch-Henle postulates' linking a single virulence factor to host response induction.
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| 7. |
- Areschoug, Thomas, et al.
(författare)
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Scavenger receptors: role in innate immunity and microbial pathogenesis.
- 2009
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Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 11, s. 1160-1169
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Tidskriftsartikel (refereegranskat)abstract
- Summary Accumulating evidence shows that many scavenger receptors (SR), including SR-A, MARCO and CD36, represent an important part of the innate immune defence by acting as pattern-recognition receptors (PRR), in particular against bacterial pathogens. Several SR are expressed on macrophages and dendritic cells, where they act as phagocytic receptors mediating non-opsonic phagocytosis of pathogenic microbes. Another important function of some SR is to act as co-receptors to TLRs, modulating the inflammatory response to TLR agonists. On bacteria, the SR ligands have commonly been reported to be LPS and LTA, but recent advances in the field indicate that bacterial surface proteins play a more important role as target molecules for SR than previously thought. Interestingly, recent data show that major pathogens, including Streptococcus pyogenes and the group B streptococcus (GBS), have evolved mechanisms to evade SR-mediated recognition. Moreover, intracellular pathogens, such as hepatitis C virus (HCV) and Plasmodium falciparum, utilize the SR to gain entry into host cells, focusing interest on the importance of SR also in the molecular pathogenesis of infectious diseases. This review highlights the complex interactions between SR and pathogenic microbes, and discusses the role of these interactions in host defence and microbial pathogenesis.
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| 8. |
- Bergsten, Göran, et al.
(författare)
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Do type 1 fimbriae promote inflammation in the human urinary tract?
- 2007
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Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 9:7, s. 1766-1781
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 fimbriae have been implicated as virulence factors in animal models of urinary tract infection (UTI), but the function in human disease remains unclear. This study used a human challenge model to examine if type 1 fimbriae trigger inflammation in the urinary tract. The asymptomatic bacteriuria strain Escherichia coli 83972, which fails to express type 1 fimbriae, due to a 4.25 kb fimB-fimD deletion, was reconstituted with a functional fim gene cluster and fimbrial expression was monitored through a gfp reporter. Each patient was inoculated with the fim+ or fim- variants on separate occasions, and the host response to type 1 fimbriae was quantified by intraindividual comparisons of the responses to the fim+ or fim- isogens, using cytokines and neutrophils as end-points. Type 1 fimbriae did not promote inflammation and adherence was poor, as examined on exfoliated cells in urine. This was unexpected, as type 1 fimbriae enhanced the inflammatory response to the same strain in the murine urinary tract and as P fimbrial expression by E. coli 83972 enhances adherence and inflammation in challenged patients. We conclude that type 1 fimbriae do not contribute to the mucosal inflammatory response in the human urinary tract.
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| 9. |
- Fischer, Hans, et al.
(författare)
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Ceramide as a TLR4 agonist; a putative signalling intermediate between sphingolipid receptors for microbial ligands and TLR4.
- 2007
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Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 9:5, s. 1239-1251
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Tidskriftsartikel (refereegranskat)abstract
- Mucosal Toll-like receptors (TLRs) respond to pathogens, but remain inert to the indigenous flora, suggesting that the TLRs can receive pathogen-specific signals. For example, TLR4 signalling is activated in CD14-negative epithelial cells by P-fimbriated, uropathogenic Escherichia coli, but not by lipopolysaccharide. The fimbriae use glycosphingolipids as recognition receptors and there is release of ceramide, which is the membrane-anchoring domain of the receptors. In this study, ceramide was identified as a TLR4 agonist and as a putative signalling intermediate between the glycosphingolipid recognition receptors and TLR4. Exogenous ceramide activated a TLR4-dependent epithelial cell response, as shown by exposing stably transfected TLR4-positive or -negative human embryonal kidney cells to C2 and C6 ceramide. A similar, TLR4-dependent response occurred after deliberate release of endogenous long-chained ceramide with sphingomyelinase. Microbial ligands with glycosphingolipid specificity (P fimbriae or the B subunit of Shiga toxin) were shown to increase the levels of ceramide and to trigger a TLR4-dependent response in epithelial cells. The results show that ceramide activates TLR4 signalling and suggest that this mechanism might allow pathogens to elicit mucosal TLR4 responses by perturbing sphingolipid receptors for virulence ligands like P fimbriae.
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| 10. |
- John, Constance M, et al.
(författare)
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Galectin-3 binds lactosaminylated lipooligosaccharides from Neisseria gonorrhoeae and is selectively expressed by mucosal epithelial cells that are infected
- 2002
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Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 4:10, s. 649-661
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Tidskriftsartikel (refereegranskat)abstract
- Galectins are a family of beta-galactoside binding proteins that have been proposed as host receptors for bacteria because beta-galactoside carbohydrates are common in bacterial membrane glycolipid lipooligosaccharides (LOS) and lipopolysaccharides. We investigated the interaction of galectin-3 with gonococcal LOS that make lactosyl (Lc(2) or Lac), paraglobosyl (nLc(4) ; LNnT; lacto-N -neotetraose), gangliosyl (IV3 GalNAcnLc(4) ), and neolactohexaosyl (nLc(6) , lactonorhexaosyl) oligosaccharides. All but gangliosyl LOS terminate in beta-galactoside. Galectin-3 had the highest affinity for the nLc(6) LOS, which is made by a strain that is highly infectious for the male urethra, but also bound nLc(4) LOS and to a Lac LOS. The lacto-N -neotetraose tetrasaccharide was a more potent inhibitor of galectin-3 binding to LOS than either lactose or N -acetyllactosamine. The relative affinity of galectin-3 for gonococci mirrored its affinity for purified LOS. Western blot analysis revealed expression of galectin-3 by human endometrial adenocarcinoma and prostatic epithelial cells that can be invaded by gonococci. Immunohistochemistry of human fallopian tube epithelium showed localized expression of galectin-3 by non-ciliated cells, the specific cell gonococci invade in this tissue. We conclude that because of its location and affinity for gonococcal LOS galectin-3 could play a role in gonococcal infection.
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