The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20070563
The Journal of Experimental Medicine, Vol. 204, No. 8, 1891-1900
The Rockefeller University Press, 0022-1007 $30.00
© Brandl et al.
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ARTICLE

MyD88-mediated signals induce the bactericidal lectin RegIII{gamma} and protect mice against intestinal Listeria monocytogenes infection

Katharina Brandl1, George Plitas2, Bernd Schnabl3, Ronald P. DeMatteo2, and Eric G. Pamer1

1 Infectious Diseases Service, Department of Medicine, Immunology Program, Sloan-Kettering Institute, 2 Hepatobiliary Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021
3 Department of Medicine, Columbia University, New York, NY 10032

Listeria monocytogenes is a food-borne bacterial pathogen that causes systemic infection by traversing the intestinal mucosa. Although MyD88-mediated signals are essential for defense against systemic L. monocytogenes infection, the role of Toll-like receptor and MyD88 signaling in intestinal immunity against this pathogen has not been defined. We show that clearance of L. monocytogenes from the lumen of the distal small intestine is impaired in MyD88–/– mice. The distal ileum of wild-type (wt) mice expresses high levels of RegIII{gamma}, which is a bactericidal lectin that is secreted into the bowel lumen, whereas RegIII{gamma} expression in MyD88–/– mice is nearly undetectable. In vivo depletion of RegIII{gamma} from the small intestine of wt mice diminishes killing of luminal L. monocytogenes, whereas reconstitution of MyD88-deficient mice with recombinant RegIII{gamma} enhances intestinal bacterial clearance. Experiments with bone marrow chimeric mice reveal that MyD88-mediated signals in nonhematopoietic cells induce RegIII{gamma} expression in the small intestine, thereby enhancing bacterial killing. Our findings support a model of MyD88-mediated epithelial conditioning that protects the intestinal mucosa against bacterial invasion by inducing RegIII{gamma}.


Abbreviations used: Defcr, Defensin-related cryptdin; LLO, listeriolysin O; MLN, mesenteric lymph node; p.i., post-infection; TLR, Toll-like receptor; rs, related sequence.


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