Roles for Autophagy Proteins in Immunity and Host Defense

Abstract

There is a clear link between defects in autophagy and the development of autoimmune and chronic inflammatory diseases, raising interest in better understanding the roles of autophagy within the immune system. In addition, autophagy has been implicated in the immune response to infection by pathogenic microbes. As such, there are efforts currently underway to develop modulators of autophagy as a therapeutic strategy for the treatment of the autoimmune, inflammatory, and infectious diseases. In this review, we discuss the numerous roles for autophagy in immunity and how these activities are linked to disease. We highlight how autophagy affects pathogen clearance, phagocytosis, pattern recognition receptor signaling, inflammation, antigen presentation, cell death, and immune cell development and maintenance. With these diverse and extensive immune-related functions for autophagy in mind, we finish by considering the possible implications of targeting autophagy as a therapeutic strategy.

Loss of murine Paneth cell function alters the immature intestinal microbiome and mimics changes seen in neonatal necrotizing enterocolitis

“…Recent studies have elucidated secretory autophagy as a mechanism of Paneth cell granule release [ 39 – 41 ]. Mice lacking a normal autophagy pathway have decreased Paneth cell lysozyme granule secretion and defects in bacterial clearance [ 42 ].…”

Autophagy: Supporting cellular and organismal homeostasis by self-eating

“…Autophagy is also involved in antigen presentation by MHC-II molecules in macrophages, dendritic cells and thymic epithelial cells. Autophagosomes containing degraded pathogens or intracellular antigens fuse with the cellular compartments where MHC-II loading occurs (Kinsella et al, 2018;Paludan et al, 2005;Schmid et al, 2007). A recent study revealed yet another aspect in the interplay between autophagy and immunity.…”

“…In a mouse model of autoimmune disease, the inability of T cells to upregulate autophagy decreased the severity of the disease (Mocholi et al, 2018). Finally, autophagy genes have been demonstrated to play different roles during the development of both B cells and T cells (Kinsella et al, 2018).…”

“…Mouse models of Crohn's disease were used to show that ATG16L1 can control inflammasome activation (Cadwell et al, 2008;Saitoh et al, 2008). Mutations in ATG16L1 are also associated with defects in innate immune response against enteric bacteria (Kinsella et al, 2018;Strisciuglio et al, 2013). Further, a missense mutation in the autophagy receptor NDP52 is also associated with Crohn's disease (Ellinghaus et al, 2013).…”

Multifaceted Roles of Autophagy in Health and Disease

“…In addition, polymorphisms in autophagy-related genes have been associated with autoimmune and inflammatory diseases, with the most notable association being ATG16L1 polymorphisms and Crohn's disease. 1 The diverse roles of autophagy in the immune system highlight the fundamental importance of this pathway in both health and disease and the complexity of interactions between autophagy and other cellular processes.…”