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Mycobacterium tuberculosis Elevates SLIT2 Expression Within the Host and Contributes to Oxidative Stress Responses During Infection

Borbora, SM and Satish, BA and Sundar, S and Mahima, Mahima and Bhatt, S and Balaji, KN (2023) Mycobacterium tuberculosis Elevates SLIT2 Expression Within the Host and Contributes to Oxidative Stress Responses During Infection. In: Journal of Infectious Diseases, 228 (5). pp. 519-532.

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Official URL: https://doi.org/10.1093/infdis/jiad126


During infection, Mycobacterium tuberculosis (Mtb) rewires distinct host signaling pathways, resulting in pathogen-favorable outcomes. Oxidative stress build-up is a key cellular manifestation that occurs due to the cumulative effect of elevated reactive oxygen species (ROS) generation and the inept ability of the cell to mitigate ROS levels. Here, we report the Mtb-induced expression of the neuronal ligand SLIT2 to be instrumental in ROS accumulation during infection. Loss-of-function analysis revealed the heightened expression of SLIT2 to be dependent on the Mtb-mediated phosphorylation of the P38/JNK pathways. Activation of these kinases resulted in the loss of the repressive H3K27me3 signature on the Slit2 promoter. Furthermore, SLIT2 promoted the expression of Vanin1 (VNN1), which contributed to copious levels of ROS within the host. Thus, we dissect the pathway leading to the robust expression of SLIT2 during Mtb infection while outlining the potential consequences of SLIT2 upregulation in infected macrophages. © 2023 The Author(s). Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved.

Item Type: Journal Article
Publication: Journal of Infectious Diseases
Publisher: Oxford University Press
Additional Information: The Copyright for this article belongs to the Oxford University Press.
Keywords: acetylcysteine; glutathione; histone H3; Janus kinase; mitogen activated protein kinase p38; reactive oxygen metabolite; Slit2 protein; small interfering RNA, animal model; Article; bioinformatics; chromatin immunoprecipitation; colony forming unit; controlled study; DNA methylation; enzyme activity; female; fluorescence microscopy; gene expression; immunoblotting; immunofluorescence assay; immunoprecipitation; in vitro study; in vivo study; JNK signaling; macrophage; male; MAPK signaling; mouse; Mycobacterium tuberculosis; nonhuman; oxidative stress; protein expression; protein phosphorylation; real time polymerase chain reaction; RNA isolation; tuberculosis; upregulation
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 09 Nov 2023 10:00
Last Modified: 09 Nov 2023 10:00
URI: https://eprints.iisc.ac.in/id/eprint/83317

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