Mycobacterium tuberculosis elevates SLIT2 expression within the host and contributes to oxidative stress responses during infection.

During infection, Mycobacterium tuberculosis (Mtb) rewires distinct host signaling pathways that results 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 generation (ROS) 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), that 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.© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Citation

Salik Miskat Borbora, Bijewar Ashish Satish, Smriti Sundar, Mahima B, Sneha Bhatt, Kithiganahalli Narayanaswamy Balaji. Mycobacterium tuberculosis elevates SLIT2 expression within the host and contributes to oxidative stress responses during infection. The Journal of infectious diseases. 2023 May 09

PMID: 37158474

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