Pre-existing mycobacterial infection modulates Candida albicans-driven pyroptosis

Bhatt, B and Prakhar, P and Lohia, GK and Rajmani, RS and Balaji, KN (2022) Pre-existing mycobacterial infection modulates Candida albicans-driven pyroptosis. In: FEBS Journal, 289 (6). 1536 -1551.

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Abstract

Active tuberculosis patients are at high risk of coinfection with opportunistic fungal pathogen Candida albicans. However, the molecular mechanisms that orchestrate pathogenesis of Mycobacterium tuberculosis (Mtb)-C. albicans coinfection remain elusive. In the current study, we utilize a mouse model to demonstrate that Mtb promotes a macrophage environment that is conducive for C. albicans survival. Mtb-dependent protein kinase Cζ-WNT signalling axis induces expression of an E3 ubiquitin ligase, constitutive photomorphogenesis protein 1 (COP1). A secondary infection of C. albicans in such Mtb-infected macrophages causes COP1 to mediate the proteasomal degradation of interferon regulatory factor 9 (IRF9), a cardinal factor that we identified to arbitrate an inflammatory programmed cell death, pyroptosis. In vivo experiments mimicking a pre-existing Mtb infection demonstrate that inhibition of pyroptosis in mice results in increased C. albicans burden and aberrant lung tissue architecture, leading to increased host mortality. Together, our study reveals the crucial role of pyroptosis regulation for manifesting a successful C. albicans–Mtb coinfection.

Item Type:	Journal Article
Publication:	FEBS Journal
Publisher:	John Wiley and Sons Inc
Additional Information:	The copyright for this article belongs to the John Wiley and Sons Inc
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology Division of Biological Sciences > Centre for Infectious Disease Research
Date Deposited:	18 Nov 2021 09:36
Last Modified:	16 Jun 2022 06:59
URI:	https://eprints.iisc.ac.in/id/eprint/70583

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