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

PLoS Pathogens
Christin FriedrichMatthias Lochner

Abstract

MyD88-mediated signaling downstream of Toll-like receptors and the IL-1 receptor family is critically involved in the induction of protective host responses upon infections. Although it is known that MyD88-deficient mice are highly susceptible to a wide range of bacterial infections, the cell type-specific contribution of MyD88 in protecting the host against intestinal bacterial infection is only poorly understood. In order to investigate the importance of MyD88 in specific immune and nonimmune cell types during intestinal infection, we employed a novel murine knock-in model for MyD88 that enables the cell type-specific reactivation of functional MyD88 expression in otherwise MyD88-deficient mice. We report here that functional MyD88 signaling in CD11c+ cells was sufficient to activate intestinal dendritic cells (DC) and to induce the early group 3 innate lymphoid cell (ILC3) response as well as the development of colonic Th17/Th1 cells in response to infection with the intestinal pathogen C. rodentium. In contrast, restricting MyD88 signaling to several other cell types, including macrophages (MO), T cells or ILC3 did not induce efficient intestinal immune responses upon infection. However, we observed that the functional expr...Continue Reading

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Citations

Sep 12, 2019·Immunology·Amelia T Soderholm, Virginia A Pedicord
Feb 28, 2020·Nature Reviews. Gastroenterology & Hepatology·Juan F Burgueño, Maria T Abreu
Sep 22, 2019·Nature Reviews. Microbiology·Caroline Mullineaux-SandersGad Frankel
Jun 20, 2020·Cancer Immunology, Immunotherapy : CII·Brittany L BunchJoseph Markowitz
Jan 9, 2021·Frontiers in Immunology·Ingrid Kazue Mizuno WatanabeNiels Olsen Saraiva Câmara
Sep 2, 2021·Mucosal Immunology·Cécilia LucianiHugues Lelouard

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Methods Mentioned

BETA
flow cytometry
transgenic
PCR
IEC
FACS

Software Mentioned

R
QIIME
FlowJo
PyNAST
Cluster
Nuance
JavaTree
UCLUST
GraphPad Prism
PHYLOSEQ

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