PUBLICATION

Mycobacterial CpsA activates type I IFN signaling in macrophages via cGAS-mediated pathway

Authors: Ding, Y., Tong, J., Luo, G., Sun, R., Bei, C., Feng, Z., Meng, L., Wang, F., Zhou, J., Chen, Z., Li, D., Fan, Y., Song, S., Wang, D., Feng, C.G., Liu, H., Chen, Q., Yan, B., Gao, Q.
ID: ZDB-PUB-240520-8
Date: 2024
Source: iScience 27: 109807109807 (Journal)
Registered Authors
Keywords: Immunology, Microbiology, Molecular microbiology
MeSH Terms: none
PubMed: 38766355 Full text @ iScience

Abstract

Type I interferon (IFN) production is crucial in tuberculosis pathogenesis, yet the bacterial factors initiating this process are incompletely understood. CpsA, protein of Mycobacterium marinum and Mycobacterium tuberculosis, plays a key role in maintaining bacterial virulence and inhibiting host cell LC3-associated phagocytosis. By utilizing CpsA full deletion mutant studies, we re-verified its essential role in infection-induced pathology and revealed its new role in type I IFN expression. CpsA deficiency hindered IFN production in infected macrophages in vitro as well as zebrafish and mice in vivo. This effect was linked to the cGAS-TBK1-IRF3 pathway, as evidenced by decreased TBK1 and IRF3 phosphorylation in CpsA-deficient bacterial strain-infected macrophages. Moreover, we further show that CpsA deficiency cause decreased cytosolic DNA levels, correlating with impaired phagosomal membrane rupture. Our findings reveal a new function of mycobacterial CpsA in type I IFN production and offer insight into the molecular mechanisms underlying mycobacterial infection pathology.

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