Critical role for MyD88-mediated neutrophil recruitment during Clostridium difficile colitis Journal Article


Authors: Jarchum, I.; Liu, M.; Shi, C.; Equinda, Michele; Pamer, E. G.
Article Title: Critical role for MyD88-mediated neutrophil recruitment during Clostridium difficile colitis
Abstract: Clostridium difficile can infect the large intestine and cause colitis when the normal intestinal microbiota is altered by antibiotic administration. Little is known about the innate immune signaling pathways that marshal inflammatory responses to C. difficile infection and whether protective and pathogenic inflammatory responses can be dissociated. Toll-like receptors predominantly signal via the MyD88 adaptor protein and are important mediators of innate immune signaling in the intestinal mucosa. Here, we demonstrate that MyD88-mediated signals trigger neutrophil and CCR2-dependent Ly6C hi monocyte recruitment to the colonic lamina propria (cLP) during infection, which prevent dissemination of bystander bacteria to deeper tissues. Mortality is markedly increased in MyD88-deficient mice following C. difficile infection, as are parameters of mucosal tissue damage and inflammation. Antibody-mediated depletion of neutrophils markedly increases mortality, while attenuated recruitment of Ly6C hi monocytes in CCR2-deficient mice does not alter the course of C. difficile infection. Expression of CXCL1, a neutrophilrecruiting chemokine, is impaired in the cLP of MyD88 -/- mice. Our studies suggest that MyD88-mediated signals promote neutrophil recruitment by inducing expression of CXCL1, thereby providing critical early defense against C. difficile-mediated colitis. © 2012, American Society for Microbiology.
Keywords: signal transduction; survival analysis; mortality; nonhuman; mouse; animals; mice; mice, knockout; animal experiment; inflammation; mice, inbred c57bl; neutrophil; neutrophils; clostridium difficile infection; monocytes; clostridium difficile; tissue injury; myeloid differentiation factor 88; chemokine receptor ccr2; cxcl1 chemokine; mucous membrane; intestinal mucosa; enterocolitis, pseudomembranous; lamina propria; chemokine cxcl1; neutrophil infiltration
Journal Title: Infection and Immunity
Volume: 80
Issue: 9
ISSN: 0019-9567
Publisher: American Society for Microbiology  
Date Published: 2012-09-01
Start Page: 2989
End Page: 2996
Language: English
DOI: 10.1128/iai.00448-12
PROVIDER: scopus
PMCID: PMC3418725
PUBMED: 22689818
DOI/URL:
Notes: --- - "Export Date: 2 November 2012" - "CODEN: INFIB" - "Source: Scopus"
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MSK Authors
  1. Eric Pamer
    278 Pamer
  2. Mingyu Liu
    3 Liu
  3. Chao Shi
    14 Shi