論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 16 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 7.0 |
| リソース情報 | |
| 実験動物マウス | RBRC00858 |