Innate immune signals triggered on organelle membranes.

Abstract

Our body is constantly exposed to pathogens, and equipped with a highly elaborate immune system to fight against invading pathogens. The first line of defense is the innate immune system. It has evolved to detect conserved microbial molecular patterns, dubbed pathogen-associated molecular patterns (PAMPs), through pattern recognition receptors (PRRs). The binding of PRRs to PAMPs activates intracellular signalling cascades that lead to the expression of proinflammatory cytokines, type I interferons, and other antiviral proteins that all coordinate the elimination of pathogens and infected cells. PRRs can be classified as transmembrane receptors, including Toll-like receptors (TLRs) and some C-type lectin receptors (CLRs), and as cytosolic receptors including retinoic acid-inducible gene-I (RIG-I)-like receptors, nucleotide-binding domain and leucine-rich repeat-containing (NLR) proteins, and cyclic GMP-AMP (cGAMP) synthase (cGAS). Studies have revealed that innate immune signals, including the ones activated by cytosolic PRRs, are triggered on organelle membranes. Here we review the recent insights into how organelle membranes and their associated membrane lipids contribute to PRR-mediated innate immune signals.