RRC ID 56696
Author Benmerzoug S, Bounab B, Rose S, Gosset D, Biet F, Cochard T, Xavier A, Rouxel N, Fauconnier L, Horsnell WGC, Ryffel B, Togbe D, Quesniaux VFJ.
Title Sterile Lung Inflammation Induced by Silica Exacerbates Mycobacterium tuberculosis Infection via STING-Dependent Type 2 Immunity.
Journal Cell Rep
Abstract Lung inflammation induced by silica impairs host control of tuberculosis, yet the underlying mechanism remains unclear. Here, we show that silica-driven exacerbation of M. tuberculosis infection associates with raised type 2 immunity. Silica increases pulmonary Th2 cell and M2 macrophage responses, while reducing type 1 immunity after M. tuberculosis infection. Silica induces lung damage that prompts extracellular self-DNA release and activates STING. This STING priming potentiates M. tuberculosis DNA sensing by and activation of cGAS/STING, which triggers enhanced type I interferon (IFNI) response and type 2 immunity. cGAS-, STING-, and IFNAR-deficient mice are resistant to silica-induced exacerbation of M. tuberculosis infection. Thus, silica-induced self-DNA primes the host response to M. tuberculosis-derived nucleic acids, which increases type 2 immunity while reducing type 1 immunity, crucial for controlling M. tuberculosis infection. These data show how cGAS/STING pathway activation, at the crossroads of sterile inflammation and infection, may affect the host response to pathogens such as M. tuberculosis.
Volume 27(9)
Pages 2649-2664.e5
Published 2019-5-28
DOI 10.1016/j.celrep.2019.04.110
PII S2211-1247(19)30600-X
PMID 31141689
MeSH Animals Dendritic Cells Host-Pathogen Interactions / immunology* Immunity, Innate / immunology* Interferon Regulatory Factor-3 / physiology Interferon Type I / metabolism Macrophages / immunology Macrophages / microbiology Macrophages / pathology Membrane Proteins / physiology* Mice Mice, Inbred C57BL Mice, Knockout Mycobacterium tuberculosis / immunology* Nucleotidyltransferases / physiology Pneumonia / chemically induced Pneumonia / complications* Receptor, Interferon alpha-beta / physiology Signal Transduction Silicon Dioxide / toxicity* Tuberculosis / etiology* Tuberculosis / metabolism Tuberculosis / pathology
IF 7.815
Times Cited 5
Resource
Mice B6;129S6-Bcl2l12/Irf3/TtgRbrc(RBRC00858)