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The intracellular pathogen, Mycobacterium tuberculosis (M. tb) uses various mechanisms to evade its demise. One of such mechanisms is phagosomal damage and subsequent cytosolic translocation. This damage is recognized and targeted by the host’s bactericidal autophagy pathway. It is suggested that cytosolic translocation of M. tb is time-dependent, occurring at later time points of 48 to 72 hours post-infection. It is, however, not known whether increased autophagic targeting correlates with these later time points of infection. Here, we investigated the time and infection-dependent profile of autophagy activity through the course of M. tb infection in mammalian macrophages. Autophagy activity was inferred by the turnover measurement of autophagy markers and M. tb bacilli in THP-1 and RAW 264.7 macrophages. Over a period of 4 to 72 hours, we observed the highest autophagy turnover at 48 hours of infection in bacteria-containing subpopulations of infected cells. This was evident by the highest turnover levels of p62 and intracellular M. tb bacilli. These observations support the notion that phagosomal damage mostly occurs at this time point and reveal the correlation of increased autophagy activity. The findings support the preservation of autophagy activity despite M. tb infection while also highlighting time-dependent differences in M. tb-infected macrophages. Future studies may further explore time-dependent exogenous autophagy targeting towards host-directed anti-tuberculosis therapy. Finally, this study supports the exploration of LC3B and p62 as suitable and sensitive biomarkers in Tuberculosis infection. |
