Mycobacteria modulate SUMOylation to suppresses protective responses in dendritic cells.

Autor: Anang V; Infectious Disease Immunology Lab, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India., Singh A; Infectious Disease Immunology Lab, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India., Kumar Rana A; Infectious Disease Immunology Lab, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India., Saraswati SSK; Infectious Disease Immunology Lab, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India., Bandyopadhyay U; Infectious Disease Immunology Lab, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India., Verma C; Infectious Disease Immunology Lab, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India., Chadha A; Infectious Disease Immunology Lab, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India., Natarajan K; Infectious Disease Immunology Lab, Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2023 Sep 29; Vol. 18 (9), pp. e0283448. Date of Electronic Publication: 2023 Sep 29 (Print Publication: 2023).
DOI: 10.1371/journal.pone.0283448
Abstrakt: Post translational modifications (PTMs) are exploited by various pathogens in order to escape host immune responses. SUMOylation is one of the PTMs which is involved in regulation of a variety of cellular responses. However, the effects of host SUMOylation on pathogenic bacteria largely remain elusive. We, therefore, investigated the role of SUMOylation in regulating defense responses in dendritic cells (DCs) during mycobacterial infection. Dendritic Cells of female BALB/c mice and THP-1 macrophages were used. Western blotting was performed to measure the expression of level of SUMO1, pSTAT1, pp38, pERK, Beclin-1, LC3, Bax and Cytochrome C. For bacterial burden confocal microscopy and CFU (Colony Forming Unit) were used. Flow cytometry was used for ROS and co-stimulatory molecules measurement. Cytokine level were measured using ELISA. We show that stimulation of Bone Marrow Derived Dendritic Cells (BMDCs) with mycobacterial antigen Rv3416 or live infection with Mycobacterium bovis BCG increases the SUMOylation of host proteins. Inhibition of SUMOylation significantly decreased intracellular bacterial loads in DCs. Additionally, inhibiting SUMOylation, induces protective immune responses by increasing oxidative burst, pro-inflammatory cytokine expression and surface expression of T cell co-stimulatory molecules, and activation of pSTAT1 and Mitogen Activated Protein Kinases (MAPK) proteins- pp38 and pERK. SUMOylation inhibition also increased apoptosis and autophagy in BMDCs. Intriguingly, mycobacteria increased SUMOylation of many of the above molecules. Furthermore, inhibiting SUMOylation in DCs primed T cells that in turn attenuated bacterial burden in infected macrophages. These findings demonstrate that SUMOylation pathway is exploited by mycobacteria to thwart protective host immune responses.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Anang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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