MyD88-mediated signals induce the bactericidal lectin RegIIIγ and protect mice against intestinal Listeria monocytogenes infection

Abstract

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 RegIIIγ, which is a bactericidal lectin that is secreted into the bowel lumen, whereas RegIIIγ expression in MyD88−/− mice is nearly undetectable. In vivo depletion of RegIIIγ from the small intestine of wt mice diminishes killing of luminal L. monocytogenes, whereas reconstitution of MyD88-deficient mice with recombinant RegIIIγ enhances intestinal bacterial clearance. Experiments with bone marrow chimeric mice reveal that MyD88-mediated signals in nonhematopoietic cells induce RegIIIγ 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 RegIIIγ.

MyD88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific EGF receptor ligands

“…In the setting of an acute infectious intestinal inflammation, we have shown previously for L. monocytogenes and vancomycinresistant Enterococcus faecium that MyD88 signaling plays an important role in nonhematopoietic cells by inducing the antimicrobial molecule RegIIIγ, which is important for defense against Gram-positive bacteria (22,25). In line with these results, we find now that TLR signaling in nonhematopoietic cells is crucial in a model of DSS-induced colitis.…”

Nod2 is required for the regulation of commensal microbiota in the intestine

“…Therefore, it is tempting to speculate that mutations in the Nod2 gene in Crohn's disease are associated with changes in the composition and load of the commensal microbiota in the terminal ileum that may facilitate disease progression and pathology. MyD88 also is known to control intestinal infection by pathogenic bacteria such as Listeria monocytogenes or vancomycin-resistant Enterococcus through an increased expression of antimicrobials (32,33). Interestingly, Paneth cell-intrinsic expression of MyD88 has Fresh feces samples were collected from mice at 0, 3, 7, and 14 days after inoculation, and DNA was purified.…”

Yip1 domain family, member 6 (Yipf6) mutation induces spontaneous intestinal inflammation in mice

“…Generation of BM chimeric mice was performed as described (19)(20)(21). Recipient WT (CD45.1) or Klein-Zschocher (CD45.2) mice were lethally irradiated with 950 rads using a 137 Cs source and injected i.v.…”