Sterile Lung Inflammation Induced by Silica Exacerbates Mycobacterium tuberculosis Infection via STING-Dependent Type 2 Immunity

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.
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Submitted on : Tuesday, June 4, 2019 - 2:38:58 PM
Last modification on : Tuesday, June 11, 2019 - 4:41:37 PM

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Sulayman Benmerzoug, Badreddine Bounab, Stephanie Rose, David Gosset, Franck Biet, et al.. Sterile Lung Inflammation Induced by Silica Exacerbates Mycobacterium tuberculosis Infection via STING-Dependent Type 2 Immunity. Cell Reports , Elsevier Inc, 2019, 27 (9), pp.2649-2664.e5. ⟨10.1016/j.celrep.2019.04.110⟩. ⟨hal-02147129⟩

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