Suppressive effects of toll-like receptor 2, toll-like receptor 4, and toll-like receptor 7 on protective responses to Mycobacterium bovis BCG from epithelial cells.

Autor: Singh A; Infectious Disease Immunology Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, 110007, India. Electronic address: aarti1kdn@gmail.com., Singh A; Infectious Disease Immunology Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, 110007, India., Saraswati SSK; Infectious Disease Immunology Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, 110007, India., Rana AK; Infectious Disease Immunology Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, 110007, India., Singh A; Infectious Disease Immunology Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, 110007, India., Verma C; Infectious Disease Immunology Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, 110007, India., Sinha V; Infectious Disease Immunology Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, 110007, India., Kalra K; Infectious Disease Immunology Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, 110007, India., Natarajan K; Infectious Disease Immunology Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, 110007, India. Electronic address: knatarajan@acbr.du.ac.in.
Jazyk: angličtina
Zdroj: Microbes and infection [Microbes Infect] 2024 Oct 04, pp. 105428. Date of Electronic Publication: 2024 Oct 04.
DOI: 10.1016/j.micinf.2024.105428
Abstrakt: Mycobacteria have several mechanisms for evasion of protective responses mounted by the host. In this study, we unravel yet another mechanism that is mediated by Toll-Like Receptors TLR2, TLR4, and TLR7 in epithelial cells. We show that mycobacterial infection of epithelial cells increases the expression of TLR2, TLR4, and TLR7. Stimulation of either TLR along with mycobacterial infection results in an inhibition of oxidative burst resulting in increased survival of mycobacteria inside epithelial cells. TLR stimulation along with mycobacterial infection also inhibits activation of epithelial cells for T cell responses by differentially regulating the activation of ERK-MAPK and p38-MAPK along with inhibition of co-stimulatory molecule CD86 expression. Furthermore, stimulation of either TLR inhibits the induction of apoptosis and autophagy. Knockdown of either TLR by specific siRNAs reverses the inhibition by ROS and apoptosis by mycobacteria and results in reduced intracellular survival of mycobacteria in a MyD88-dependent manner. These results point towards a negative role for TLR2, TLR4, and TLR7 in regulating protective responses to M. bovis BCG infection in epithelial cells.
Competing Interests: Declaration of competing interest The authors declare no conflicts of interest with the content of this article.
(Copyright © 2024 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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