Autophagy is a highly controlled process in which cellular components are self-degraded and subsequently recycled. This pathway in part plays a “house cleaning” role in the cell, directing numerous cargoes to the lysosome (or the vacuole in yeast and plants) for degradation. Depending on the specific conditions, the cargoes include random portions of cytoplasm, protein aggregates, and damaged or superfluous organelles such as mitochondria and peroxisomes. Dysfunction of autophagy is linked with many pathologies, including cancer, diabetes, myopathies, heart, liver and lung diseases, and certain types of neurodegenerative disease (Castets et al., 2013; Gonzalez et al., 2011; Klionsky and Codogno, 2013; Murrow and Debnath, 2013; Rubinsztein et al., 2012; Yang and Klionsky, 2010).
Emerging studies have revealed that autophagy plays important roles in immunity. In 2004, independent studies demonstrated for the first time that invading pathogens can be cargoes for autophagy (Gutierrez et al., 2004; Nakagawa et al., 2004). Today it is well accepted that autophagy can directly eliminate intracellular pathogens, including bacteria, fungal parasites, and viruses. Autophagy can also activate innate immune signaling cascades such as Toll-like receptor (TLR) signaling to attack invading pathogens (Lee et al., 2007; Xu et al., 2007). However, microbes constantly undergo strong selective pressure to develop strategies to block host defense mechanisms autophagy through distinct mechanisms (Deretic and Levine, 2009; Kuballa et al., 2012; Levine et al., 2011; Yuk et al., 2012; Zhou and Zhang, 2012).
Autophagy’s role in immunity is not limited to controlling infection by direct elimination of pathogens. For example, autophagy facilitates MHC (major histocompatibility complex) antigen presentation, indicating that autophagy is involved in adaptive as well as innate immunity (English et al., 2009; Paludan et al., 2005). Moreover, defects in autophagy are associated with autoimmune diseases such as Crohn disease (Levine et al., 2011; Schroder and Tschopp, 2010; Shi et al., 2012). Thus, autophagy is an integral part of our response to infection and plays a key role in immunity. A comprehensive understanding of autophagy as it pertains to microbial infection and the molecular mechanisms that underlie the interplay between autophagy and immune signaling pathways may enable us to unravel the pathogenesis of many infectious and immune diseases, and develop more effective therapeutic strategies for their treatment.
