AUTHOR=Silwal Prashanta , Paik Seungwha , Kim Jin Kyung , Yoshimori Tamotsu , Jo Eun-Kyeong TITLE=Regulatory Mechanisms of Autophagy-Targeted Antimicrobial Therapeutics Against Mycobacterial Infection JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=Volume 11 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.633360 DOI=10.3389/fcimb.2021.633360 ISSN=2235-2988 ABSTRACT=Several autophagy-modulating agents show promise as host-directed therapeutics for Mycobacterium tuberculosis (Mtb) infection. Although the underlying molecular mechanisms by which autophagy-activating agents enhance antimicrobial responses against Mtb are unclear, modulation of innate immunity, inflammation, phago-lysosomal function, and metabolic pathways are postulated to be involved. Here, we discuss the mechanisms of action of autophagy-modulating agents with overcoming the immune escape strategies induced by Mtb pathogens. The factors and pathways that govern such mechanisms include adenosine 5′-monophosphate-activated protein kinase, Akt/mammalian TOR kinase, Wnt signaling, transcription factor EB, cathelicidins, inflammation, endoplasmic reticulum stress, and autophagy-related genes. An understanding of these mechanisms will facilitate the development of host-directed therapies against tuberculosis as well as other emerging and re-emerging infections.