Article,

MyD88 signaling in dendritic cells and the intestinal epithelium controls immunity against intestinal infection with C. rodentium

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PLOS Pathogens, 13 (5): 1-26 (May 2017)

Abstract

Author summary MyD88-dependent signaling pathways play a critical role in the protective immune response during intestinal infections. However, the significance of MyD88-mediated signaling in specific intestinal immune and nonimmune cell types for the activation of the early innate, adaptive and epithelial host responses upon infection remains poorly understood. Using a novel knock-in mouse model for MyD88, we report here that MyD88 signaling in CD11c+ dendritic cells (DC) is sufficient to activate RORγt+ group 3 innate lymphoid cells (ILC3) as well as Th17/Th1 cells in response to infection with C. rodentium. In contrast, restricting functional MyD88 signaling to several other immune cell types, including macrophages (MO), T cells and ILC3 did not result in intestinal immunity, while expression of MyD88 in intestinal epithelial cells (IEC) mainly enhanced epithelial barrier integrity. Together, our data suggest that MyD88 signaling in DC and IEC is both essential and sufficient to induce a full spectrum of host responses upon intestinal infection with C. rodentium.

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