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...
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| Format: | Article |
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Public Library of Science
2013
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| Online Access: | https://eprints.nottingham.ac.uk/2224/ |
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| author | Jafari, Nazilla V. Kuehne, Sarah A. Bryant, Clare E. Elawad, Mamoun Wren, Brendan W. Minton, Nigel P. Allan, Elaine Bajaj-Elliott, Mona |
| author_facet | Jafari, Nazilla V. Kuehne, Sarah A. Bryant, Clare E. Elawad, Mamoun Wren, Brendan W. Minton, Nigel P. Allan, Elaine Bajaj-Elliott, Mona |
| author_sort | Jafari, Nazilla V. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| 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 | 2025-11-14T18:17:18Z |
| format | Article |
| id | nottingham-2224 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T18:17:18Z |
| publishDate | 2013 |
| publisher | Public Library of Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-22242020-05-04T16:37:44Z https://eprints.nottingham.ac.uk/2224/ Clostridium difficile modulates host innate immunity via toxin-independent and dependent mechanism(s) Jafari, Nazilla V. Kuehne, Sarah A. Bryant, Clare E. Elawad, Mamoun Wren, Brendan W. Minton, Nigel P. Allan, Elaine Bajaj-Elliott, Mona 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. Public Library of Science 2013-07-29 Article PeerReviewed Jafari, Nazilla V., Kuehne, Sarah A., Bryant, Clare E., Elawad, Mamoun, Wren, Brendan W., Minton, Nigel P., Allan, Elaine and Bajaj-Elliott, Mona (2013) Clostridium difficile modulates host innate immunity via toxin-independent and dependent mechanism(s). PLoS ONE, 8 (7). e69846/1-e69846/10. ISSN 1932-6203 http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0069846 doi:10.1371/journal.pone.0069846 doi:10.1371/journal.pone.0069846 |
| spellingShingle | Jafari, Nazilla V. Kuehne, Sarah A. Bryant, Clare E. Elawad, Mamoun Wren, Brendan W. Minton, Nigel P. Allan, Elaine Bajaj-Elliott, Mona Clostridium difficile modulates host innate immunity via toxin-independent and dependent mechanism(s) |
| 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 | https://eprints.nottingham.ac.uk/2224/ https://eprints.nottingham.ac.uk/2224/ https://eprints.nottingham.ac.uk/2224/ |