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Publication : MyD88-mediated signals induce the bactericidal lectin RegIII gamma and protect mice against intestinal Listeria monocytogenes infection.

First Author  Brandl K Year  2007
Journal  J Exp Med Volume  204
Issue  8 Pages  1891-900
PubMed ID  17635956 Mgi Jnum  J:125955
Mgi Id  MGI:3760234 Doi  10.1084/jem.20070563
Citation  Brandl K, et al. (2007) MyD88-mediated signals induce the bactericidal lectin RegIII gamma and protect mice against intestinal Listeria monocytogenes infection. J Exp Med 204(8):1891-900
abstractText  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.
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