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
Citation
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. (2024) Mycobacterial CpsA activates type I IFN signaling in macrophages via cGAS-mediated pathway. iScience. 27:109807109807.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping