A role for TLR4 in Clostridium difficile infection and the recognition of surface layer proteins.
Clostridium difficile is the etiological agent of antibiotic-associated diarrhoea (AAD) and pseudomembranous colitis in humans. The role of the surface layer proteins (SLPs) in this disease has not yet been fully explored. The aim of this study was to investigate a role for SLPs in the recognition o...
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Public Library of Science (PLoS)
2011
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oai:doaj.org-article:6486bcb3a30d4095ab5596eb0047788c2021-11-18T06:03:16ZA role for TLR4 in Clostridium difficile infection and the recognition of surface layer proteins.1553-73661553-737410.1371/journal.ppat.1002076https://doaj.org/article/6486bcb3a30d4095ab5596eb0047788c2011-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21738466/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Clostridium difficile is the etiological agent of antibiotic-associated diarrhoea (AAD) and pseudomembranous colitis in humans. The role of the surface layer proteins (SLPs) in this disease has not yet been fully explored. The aim of this study was to investigate a role for SLPs in the recognition of C. difficile and the subsequent activation of the immune system. Bone marrow derived dendritic cells (DCs) exposed to SLPs were assessed for production of inflammatory cytokines, expression of cell surface markers and their ability to generate T helper (Th) cell responses. DCs isolated from C3H/HeN and C3H/HeJ mice were used in order to examine whether SLPs are recognised by TLR4. The role of TLR4 in infection was examined in TLR4-deficient mice. SLPs induced maturation of DCs characterised by production of IL-12, TNFα and IL-10 and expression of MHC class II, CD40, CD80 and CD86. Furthermore, SLP-activated DCs generated Th cells producing IFNγ and IL-17. SLPs were unable to activate DCs isolated from TLR4-mutant C3H/HeJ mice and failed to induce a subsequent Th cell response. TLR4⁻/⁻ and Myd88⁻/⁻, but not TRIF⁻/⁻ mice were more susceptible than wild-type mice to C. difficile infection. Furthermore, SLPs activated NFκB, but not IRF3, downstream of TLR4. Our results indicate that SLPs isolated from C. difficile can activate innate and adaptive immunity and that these effects are mediated by TLR4, with TLR4 having a functional role in experimental C. difficile infection. This suggests an important role for SLPs in the recognition of C. difficile by the immune system.Anthony RyanMark LynchSinead M SmithSylvie AmuHendrik J NelClaire E McCoyJennifer K DowlingEve DraperVincent O'ReillyCiara McCarthyJulie O'BrienDéirdre Ní EidhinMary J O'ConnellBrian KeoghCharles O MortonThomas R RogersPadraic G FallonLuke A O'NeillDermot KelleherChristine E LoscherPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 6, p e1002076 (2011) |
| institution |
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| collection |
DOAJ |
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| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
| spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Anthony Ryan Mark Lynch Sinead M Smith Sylvie Amu Hendrik J Nel Claire E McCoy Jennifer K Dowling Eve Draper Vincent O'Reilly Ciara McCarthy Julie O'Brien Déirdre Ní Eidhin Mary J O'Connell Brian Keogh Charles O Morton Thomas R Rogers Padraic G Fallon Luke A O'Neill Dermot Kelleher Christine E Loscher A role for TLR4 in Clostridium difficile infection and the recognition of surface layer proteins. |
| description |
Clostridium difficile is the etiological agent of antibiotic-associated diarrhoea (AAD) and pseudomembranous colitis in humans. The role of the surface layer proteins (SLPs) in this disease has not yet been fully explored. The aim of this study was to investigate a role for SLPs in the recognition of C. difficile and the subsequent activation of the immune system. Bone marrow derived dendritic cells (DCs) exposed to SLPs were assessed for production of inflammatory cytokines, expression of cell surface markers and their ability to generate T helper (Th) cell responses. DCs isolated from C3H/HeN and C3H/HeJ mice were used in order to examine whether SLPs are recognised by TLR4. The role of TLR4 in infection was examined in TLR4-deficient mice. SLPs induced maturation of DCs characterised by production of IL-12, TNFα and IL-10 and expression of MHC class II, CD40, CD80 and CD86. Furthermore, SLP-activated DCs generated Th cells producing IFNγ and IL-17. SLPs were unable to activate DCs isolated from TLR4-mutant C3H/HeJ mice and failed to induce a subsequent Th cell response. TLR4⁻/⁻ and Myd88⁻/⁻, but not TRIF⁻/⁻ mice were more susceptible than wild-type mice to C. difficile infection. Furthermore, SLPs activated NFκB, but not IRF3, downstream of TLR4. Our results indicate that SLPs isolated from C. difficile can activate innate and adaptive immunity and that these effects are mediated by TLR4, with TLR4 having a functional role in experimental C. difficile infection. This suggests an important role for SLPs in the recognition of C. difficile by the immune system. |
| format |
article |
| author |
Anthony Ryan Mark Lynch Sinead M Smith Sylvie Amu Hendrik J Nel Claire E McCoy Jennifer K Dowling Eve Draper Vincent O'Reilly Ciara McCarthy Julie O'Brien Déirdre Ní Eidhin Mary J O'Connell Brian Keogh Charles O Morton Thomas R Rogers Padraic G Fallon Luke A O'Neill Dermot Kelleher Christine E Loscher |
| author_facet |
Anthony Ryan Mark Lynch Sinead M Smith Sylvie Amu Hendrik J Nel Claire E McCoy Jennifer K Dowling Eve Draper Vincent O'Reilly Ciara McCarthy Julie O'Brien Déirdre Ní Eidhin Mary J O'Connell Brian Keogh Charles O Morton Thomas R Rogers Padraic G Fallon Luke A O'Neill Dermot Kelleher Christine E Loscher |
| author_sort |
Anthony Ryan |
| title |
A role for TLR4 in Clostridium difficile infection and the recognition of surface layer proteins. |
| title_short |
A role for TLR4 in Clostridium difficile infection and the recognition of surface layer proteins. |
| title_full |
A role for TLR4 in Clostridium difficile infection and the recognition of surface layer proteins. |
| title_fullStr |
A role for TLR4 in Clostridium difficile infection and the recognition of surface layer proteins. |
| title_full_unstemmed |
A role for TLR4 in Clostridium difficile infection and the recognition of surface layer proteins. |
| title_sort |
role for tlr4 in clostridium difficile infection and the recognition of surface layer proteins. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/6486bcb3a30d4095ab5596eb0047788c |
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