Atg8ylation as a host-protective mechanism against Mycobacterium tuberculosis

Abstract

Nearly two decades have passed since the first report on autophagy acting as a cell-autonomous defense against Mycobacterium tuberculosis. This helped usher a new area of research within the field of host-pathogen interactions and led to the recognition of autophagy as an immunological mechanism. Interest grew in the fundamental mechanisms of antimicrobial autophagy and in the prophylactic and therapeutic potential for tuberculosis. However, puzzling in vivo data have begun to emerge in murine models of M. tuberculosis infection. The control of infection in mice affirmed the effects of certain autophagy genes, specifically ATG5, but not of other ATGs. Recent studies with a more complete inactivation of ATG genes now show that multiple ATG genes are indeed necessary for protection against M. tuberculosis. These particular ATG genes are involved in the process of membrane atg8ylation. Atg8ylation in mammalian cells is a broad response to membrane stress, damage and remodeling of which canonical autophagy is one of the multiple downstream outputs. The current developments clarify the controversies and open new avenues for both fundamental and translational studies.

Dynamic Interplay of Autophagy and Membrane Repair DuringMycobacterium tuberculosisInfection

“…14 The LC3 recruitment by the LC3 lipidation on single membrane is proposed to be named atg8ylation and could be mobilized during diverse membrane associated events. 74 The only atg8ylation phenomenon described so far in the context of Mtb infection is LAP. 15 Our study failed to observe signs of LAP being induced after Mtb phagocytosis as the events of LC3 recruitment showed tubulovesicular structure formation, which is induced during canonical autophagy or xenophagy and is distinctively different from LC3 lipidation at the phagosome membrane.…”