Xenophagy: Its Role in Pathogens Infections

In pathogen infections, autophagy may selectively target microorganisms or parts thereof to control intracellular microbial proliferation/replication, a process known as xenophagy. Xenophagy can entrap and degrade microorganisms soon after their internalization, in damaged vacuoles, or after they have escaped within the cytosol. Xenophagy can also be solicited at a later time after infection, for example, to degrade newly synthesized microbial products. To recognize pathogens, cytosolic autophagy receptors (e.g. p62/SQSTM1, NBR1, NDP52, T6BP or OPTINEURIN) recognize ubiquitin-dependent or independent signals on pathogens and direct them toward a growing autophagosomal membrane. In addition, specific signal transduction pathways can boost autophagy, for example, via Toll-like receptor engagement, which could sensitize cells to promote xenophagy. In addition to canonical xenophagy which involves the engagement of core autophagy proteins to regulate the formation of an autophagosome, autophagy-associated proteins can also contribute to the degradation of phagocytosed microorganisms via a process referred to as LC3-associated phagocytosis (LAP), without the formation of a de novo autophagosome. Probably because of its tremendous contribution to the control of intracellular microorganism survival, most infectious pathogens have evolved molecular strategies to escape, exploit or even subvert xenophagy to their advantage. Pathogens can modulate the initiation of xenophagy, or one of the main steps of the autophagic process to avoid degradation and/or to facilitate their survival and/or proliferation within a cell.

Although it has become clear that xenophagy is a central cellular mechanism for combating pathogens and is considered an intrinsic immune mechanism, there is still much to be explored to fully consider the role of autophagy in infections; it will also be helpful to learn much about how cellular autophagy is regulated and how its disruption could lead to (infectious) pathologies.

This Research Topic aims to focus on the processes of xenophagy and associated LAP: how they contribute to controlling infections by pathogens, and how pathogens can escape or manipulate these antimicrobial mechanisms, in different cell types and organisms, from animals to humans.