HSP-27 and HSP-70 negatively regulate protective defence responses from macrophages during mycobacterial infection.

Autor: Saraswati SSK; Infectious Disease Immunology Laboratory, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi 110007, India. Electronic address: shakuntalatoni@gmail.com., 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., Anang V; 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., 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] 2023 Jul-Aug; Vol. 25 (6), pp. 105126. Date of Electronic Publication: 2023 Mar 16.
DOI: 10.1016/j.micinf.2023.105126
Abstrakt: Mycobacterium tuberculosis attenuates many defence responses from alveolar macrophages to create a niche at sites of infection in the human lung. Levels of Heat Shock Proteins have been reported to increase many folds in the serum of active TB patients than in latently infected individuals. Here we investigated the regulation of key defence responses by HSPs during mycobacterial infection. We show that infection of macrophages with M. bovis BCG induces higher expression of HSP-27 and HSP-70. Inhibiting HSP-27 and HSP-70 prior to mycobacterial infection leads to a significant decrease in mycobacterial growth inside macrophages. Further, inhibiting HSPs resulted in a significant increase in intracellular oxidative burst levels. This was accompanied by an increase in the levels of T cell activation molecules CD40 and IL-12 receptor and a concomitant decrease in the levels of T cell inhibitory molecules PD-L1 and IL-10 receptor. Furthermore, inhibiting HSPs significantly increased the expression of key proteins in the autophagy pathway along with increased activation of pro-inflammatory promoting transcription factors NF-κB and p-CREB. Interestingly, we also show that both HSP-27 and HSP-70 are associated with anti-apoptotic proteins Bcl-2 and Beclin-1. These results point towards a suppressive role for host HSP-27 and HSP-70 during mycobacterial infection.
Competing Interests: Declaration of competing interest The authors declare no conflicts of interest with the content of this article.
(Copyright © 2023 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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