Beyond self-eating: The control of nonautophagic functions and signaling pathways by autophagy-related proteins

Cadwell, Ken; Debnath, Jayanta

ATGs have a fundamental role in suppressing immune signaling (Cadwell, 2016) . Among the first indications that autophagy exacts inhibitory functions came from population genetic studies implicating a coding variant of ATG16L1 in Crohn's disease, a type of inflammatory bowel disease (IBD) associated with an abnormal immune response to the gut microbiota. Consistent with this genetic association, ATG16L1 deletion causes macrophages to overproduce the cytokine IL-1β, which mediates intestinal inflammation (Saitoh et al., 2008) . Although increased production of immune effectors is pathological in this setting, Atg16L1 mutation unexpectedly enhances innate immune resistance to oral infection by the Gram-negative bacterium Citrobacter rodentium (Marchiando et al., 2013) . Additionally, deletion of other ATGs throughout the autophagy pathway leads to a general increase in cytokine levels that promote resistance to influenza virus infection and inhibition of herpesvirus reactivation from latency (Park et al., 2016a) . In this section, we provide examples highlighting different mechanisms by which ATGs reduce signaling downstream of cytosolic pathogen sensors.