RRC ID |
56696
|
著者 |
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.
|
タイトル |
Sterile Lung Inflammation Induced by Silica Exacerbates Mycobacterium tuberculosis Infection via STING-Dependent Type 2 Immunity.
|
ジャーナル |
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.
|
巻・号 |
27(9)
|
ページ |
2649-2664.e5
|
公開日 |
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
|
引用数 |
5
|
リソース情報 |
実験動物マウス |
RBRC00858 |