Clostridium difficile modulates host innate immunity via toxin-independent and dependent mechanism(s).
Clostridium difficile infection (CDI) is the leading cause of hospital and community-acquired antibiotic-associated diarrhoea and currently represents a significant health burden. Although the role and contribution of C. difficile toxins to disease pathogenesis is being increasingly understood, at p...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3726775?pdf=render |
| _version_ | 1818039204847812608 |
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| author | Nazila V Jafari Sarah A Kuehne Clare E Bryant Mamoun Elawad Brendan W Wren Nigel P Minton Elaine Allan Mona Bajaj-Elliott |
| author_facet | Nazila V Jafari Sarah A Kuehne Clare E Bryant Mamoun Elawad Brendan W Wren Nigel P Minton Elaine Allan Mona Bajaj-Elliott |
| author_sort | Nazila V Jafari |
| collection | DOAJ |
| description | Clostridium difficile infection (CDI) is the leading cause of hospital and community-acquired antibiotic-associated diarrhoea and currently represents a significant health burden. Although the role and contribution of C. difficile toxins to disease pathogenesis is being increasingly understood, at present other facets of C. difficile-host interactions, in particular, bacterial-driven effects on host immunity remain less studied. Using an ex-vivo model of infection, we report that the human gastrointestinal mucosa elicits a rapid and significant cytokine response to C. difficile. Marked increase in IFN-γ with modest increase in IL-22 and IL-17A was noted. Significant increase in IL-8 suggested potential for neutrophil influx while presence of IL-12, IL-23, IL-1β and IL-6 was indicative of a cytokine milieu that may modulate subsequent T cell immunity. Majority of C. difficile-driven effects on murine bone-marrow-derived dendritic cell (BMDC) activation were toxin-independent; the toxins were however responsible for BMDC inflammasome activation. In contrast, human monocyte-derived DCs (mDCs) released IL-1β even in the absence of toxins suggesting host-specific mediation. Infected DC-T cell crosstalk revealed the ability of R20291 and 630 WT strains to elicit a differential DC IL-12 family cytokine milieu which culminated in significantly greater Th1 immunity in response to R20291. Interestingly, both strains induced a similar Th17 response. Elicitation of mucosal IFN-γ/IL-17A and Th1/Th17 immunity to C. difficile indicates a central role for this dual cytokine axis in establishing antimicrobial immunity to CDI. |
| first_indexed | 2024-12-10T07:54:55Z |
| format | Article |
| id | doaj.art-4099a747f97d483ab9ffc5b35212b8c4 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T07:54:55Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4099a747f97d483ab9ffc5b35212b8c42022-12-22T01:56:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6984610.1371/journal.pone.0069846Clostridium difficile modulates host innate immunity via toxin-independent and dependent mechanism(s).Nazila V JafariSarah A KuehneClare E BryantMamoun ElawadBrendan W WrenNigel P MintonElaine AllanMona Bajaj-ElliottClostridium difficile infection (CDI) is the leading cause of hospital and community-acquired antibiotic-associated diarrhoea and currently represents a significant health burden. Although the role and contribution of C. difficile toxins to disease pathogenesis is being increasingly understood, at present other facets of C. difficile-host interactions, in particular, bacterial-driven effects on host immunity remain less studied. Using an ex-vivo model of infection, we report that the human gastrointestinal mucosa elicits a rapid and significant cytokine response to C. difficile. Marked increase in IFN-γ with modest increase in IL-22 and IL-17A was noted. Significant increase in IL-8 suggested potential for neutrophil influx while presence of IL-12, IL-23, IL-1β and IL-6 was indicative of a cytokine milieu that may modulate subsequent T cell immunity. Majority of C. difficile-driven effects on murine bone-marrow-derived dendritic cell (BMDC) activation were toxin-independent; the toxins were however responsible for BMDC inflammasome activation. In contrast, human monocyte-derived DCs (mDCs) released IL-1β even in the absence of toxins suggesting host-specific mediation. Infected DC-T cell crosstalk revealed the ability of R20291 and 630 WT strains to elicit a differential DC IL-12 family cytokine milieu which culminated in significantly greater Th1 immunity in response to R20291. Interestingly, both strains induced a similar Th17 response. Elicitation of mucosal IFN-γ/IL-17A and Th1/Th17 immunity to C. difficile indicates a central role for this dual cytokine axis in establishing antimicrobial immunity to CDI.http://europepmc.org/articles/PMC3726775?pdf=render |
| spellingShingle | Nazila V Jafari Sarah A Kuehne Clare E Bryant Mamoun Elawad Brendan W Wren Nigel P Minton Elaine Allan Mona Bajaj-Elliott Clostridium difficile modulates host innate immunity via toxin-independent and dependent mechanism(s). PLoS ONE |
| title | Clostridium difficile modulates host innate immunity via toxin-independent and dependent mechanism(s). |
| title_full | Clostridium difficile modulates host innate immunity via toxin-independent and dependent mechanism(s). |
| title_fullStr | Clostridium difficile modulates host innate immunity via toxin-independent and dependent mechanism(s). |
| title_full_unstemmed | Clostridium difficile modulates host innate immunity via toxin-independent and dependent mechanism(s). |
| title_short | Clostridium difficile modulates host innate immunity via toxin-independent and dependent mechanism(s). |
| title_sort | clostridium difficile modulates host innate immunity via toxin independent and dependent mechanism s |
| url | http://europepmc.org/articles/PMC3726775?pdf=render |
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