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bioRxiv · 10.1101/187104

Necrosis triggered by Mycobacterium tuberculosis alters macrophage triglyceride metabolism and inflammatory response in a DGAT1-dependent manner

Jaisinghani, N.·Dawa, S.·Singh, K.·Nandy, A.·Menon, D.·Bhandari, P.·Khare, G.·Tyagi, A.·Gandotra, S.
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Abstract

Tuberculosis granulomas represent a site of controlling bacterial dissemination at the cost of host tissue damage. Within the heterogenous array of TB granulomas, some contain triglyceride (TG) rich foamy macrophages, the etiology and function of which remains largely unexplained. Here we show that necrosis of tuberculosis lesions and M. tuberculosis (Mtb) infected macrophages elicits a bystander response of triglyceride storage. We elucidate a role for the RD1 region of mycobacterial genome to be a key player in this phenomenon. TG storage in necrosis associated foamy macrophages promoted the pro-inflammatory state of macrophages while silencing expression of diacylglycerol O-acyltransferase (DGAT1) suppressed expression of pro-inflammatory genes. Surprisingly, acute infection with Mtb led to lipolysis of host TG, rather than synthesis, suggesting mobilization of triglyceride stored within macrophage lipid droplets to be involved in the inflammatory response to infection. Our data is likely to open new avenues for management of the inflammatory response during infection.

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Jaisinghani, N., Dawa, S., Singh, K., Nandy, A., Menon, D., Bhandari, P., Khare, G., Tyagi, A., Gandotra, S.. 2017-09-11. Necrosis triggered by Mycobacterium tuberculosis alters macrophage triglyceride metabolism and inflammatory response in a DGAT1-dependent manner. https://doi.org/10.1101/187104

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