Potassium ion channel Kir2.1 negatively regulates protective responses to Mycobacterium bovis BCG.

Autor:	Sinha V; Infectious Disease Immunology Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, North Campus, University Enclave, Delhi 110007, India., Singh A; Infectious Disease Immunology Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, North Campus, University Enclave, Delhi 110007, India., Singh A; Infectious Disease Immunology Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, North Campus, University Enclave, Delhi 110007, India., Saraswati SSK; Infectious Disease Immunology Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, North Campus, University Enclave, Delhi 110007, India., Rana AK; Infectious Disease Immunology Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, North Campus, University Enclave, Delhi 110007, India., Kalra K; Infectious Disease Immunology Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, North Campus, University Enclave, Delhi 110007, India., Natarajan K; Infectious Disease Immunology Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, North Campus, University Enclave, Delhi 110007, India.
Jazyk:	angličtina
Zdroj:	Journal of leukocyte biology [J Leukoc Biol] 2024 Sep 02; Vol. 116 (3), pp. 644-656.
DOI:	10.1093/jleuko/qiae068
Abstrakt:	Tuberculosis caused by the pathogen Mycobacterium tuberculosis leads to increased mortality and morbidity worldwide. The prevalence of highly drug-resistant strains has reinforced the need for greater understanding of host-pathogen interactions at the cellular and molecular levels. Our previous work demonstrated critical roles of calcium ion channels in regulating protective responses to mycobacteria. In this report, we deciphered the roles of inwardly rectifying K+ ion channel Kir2.1 in epithelial cells. Data showed that infection of epithelial cells (and macrophages) increases the surface expression of Kir2.1. This increased expression of Kir2.1 results in higher intracellular mycobacterial survival, as either inhibiting or knocking down Kir2.1 results in mounting of a higher oxidative burst leading to a significant attenuation of mycobacterial survival. Further, inhibiting Kir2.1 also led to increased expression of T cell costimulatory molecules accompanied with increased activation of MAP kinases and transcription factors nuclear factor κB and phosphorylated CREB. Furthermore, inhibiting Kir2.1 induced increased autophagy and apoptosis that could also contribute to decreased bacterial survival. Interestingly, an increased association of heat shock protein 70 kDa with Kir2.1 was observed. These results showed that mycobacteria modulate the expression and function of Kir2.1 in epithelial cells to its advantage. Competing Interests: Conflict of interest statement. None declared. (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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