MyD88-mediated signals induce in vivo production of the bactericidal lectin RegIIIγ and protect against intestinal Listeria monocytogenes infection (44.4)

Abstract

Abstract Listeria monocytogenes (L. monocytogenes) is an intracellular bacterium that causes systemic infections after traversing the intestinal mucosa. To test the hypothesis that the Toll-like receptor pathway is involved in defense against intestinal L. monocytogenes infection, we analyzed the role of the common intracellular adaptor molecule myeloid differentiation primary-response protein 88 (MyD88) following oral infection with L. monocytogenes. We found that MyD88 deficient mice have increased susceptibility to intestinal L. monocytogenes infection with higher bacterial burden in spleen, liver, mesenteric lymph nodes, intestinal lumen, and small intestine (lamina propria and intestinal epithelium). Further in vitro and in vivo studies showed that MyD88 mediated protection primarily occurs in the distal small intestine. Recently, it was shown that the intestinal bactericidal lectin RegIIIγ has antibacterial activity against L. monocytogenes. RT-PCR and Western Blot analysis of distal small intestines showed that RegIIIγ is significantly diminished in MyD88 deficient mice. Since optimal expression of RegIIIγ requires MyD88-mediated signals, our findings suggest that increased susceptibility to intestinal L. monocytogenes infection in MyD88-deficient mice results from diminished levels of this bactericidal lectin in the distal small bowel.