Clostridium difficile modulates host innate immunity via toxin-independent and dependent mechanism(s)

Nazila Jafari, Sarah A. Kuehne, Clare E. Bryant, Mamoun Elawad, Brendan W. Wren, Nigel P. Minton, Elaine Allan and Mona Bajaj-Elliott 2013. Clostridium difficile modulates host innate immunity via toxin-independent and dependent mechanism(s). PLoS ONE. 8 (7) e69846. https://doi.org/10.1371/journal.pone.0069846

TitleClostridium difficile modulates host innate immunity via toxin-independent and dependent mechanism(s)
TypeJournal article
AuthorsNazila Jafari, Sarah A. Kuehne, Clare E. Bryant, Mamoun Elawad, Brendan W. Wren, Nigel P. Minton, Elaine Allan and Mona Bajaj-Elliott
Abstract

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.

Article numbere69846
JournalPLoS ONE
Journal citation8 (7)
ISSN1932-6203
Year2013
PublisherPublic Library of Science
Publisher's version
License
CC BY 4.0
File Access Level
Open (open metadata and files)
Digital Object Identifier (DOI)https://doi.org/10.1371/journal.pone.0069846
PubMed ID23922820
Publication dates
Published29 Jul 2013

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