Regulation of Innate Immune Signaling by Autophagy

The first line of defense against infection is provided by the innate immune system, which is able to recognize molecular patterns in a variety of infectious agents through the action of different families of pattern recognition receptors (PRRs). These effectors detect the invading agent and trigger powerful inflammatory responses that help fight the infection from the very beginning. However, inflammatory reactions can be damaging for the host and must be properly controlled to prevent pathological consequences. Here we provide a comprehensive review of the important role of autophagy, a catabolic pathway that degrades cellular components for quality control and regulatory purposes, in the regulation of innate immune responses, and the underlying mechanisms involved. Inflammatory pathways discussed in this review include those triggered by Toll-like receptors (TLRs), Retinoic acid-Inducible Gene (RIG)-I-like receptors (RLRs), Nucleotide-binding Oligomerization Domain (NOD)-like receptors (NLRs), and the receptor for cyclic GMP–AMP Stimulator of Interferon Genes (STING). Finally, we also consider examples where autophagy plays context-dependent or even pro-inflammatory roles, reflecting a complex involvement that remains to be fully characterized.