Lipids that directly regulate innate immune signal transduction

Katherine C Barnett,Jonathan C Kagan

doi:10.1177/1753425919852695

Katherine C Barnett, Jonathan C Kagan

Open Access

https://doi.org/10.1177/1753425919852695

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Abstract

Pattern Recognition Receptors (PRRs) detect evidence of infection and tissue damage. The activation of these receptors and their downstream signal transduction pathways initiate a protective immune response. These signaling pathways are influenced by their spatial context, and precise subcellular positioning of proteins and protein complexes in these pathways is essential for effective immune responses in vivo. This organization is not limited to transmembrane proteins that reside in specific organelles, but also to proteins that engage membrane lipid head groups for proper positioning. In this review, we focus on the role of cell membranes and protein–lipid interactions in innate immune signal transduction and how their mechanisms of localization regulate the immune response. We will discuss how lipids spatially regulate the sensing of damage or infection, mediate effector activity, and serve as messengers of cell death and tissue damage.

Highlights

Multiple signal transduction pathways operate in the innate immune system to link microbial detection to the initiation of host defense mechanisms
At the apex of these pathways are germline-encoded protein sensors, known as Pattern Recognition Receptors (PRRs), which bind to molecular motifs common to microbes (pathogen associated molecular patterns (PAMPs)) or molecules produced during events of damage.[3]
Receptor activation through ligand binding leads to receptor oligomerization and the subsequent formation of large multiprotein signaling platforms, known as supramolecular organizing centers (SMOCs).[6]. This conclusion is supported by extensive analysis of PRR families, such as Toll-like receptors (TLRs),[7,8,9] RIG-I-like-receptors (RLRs),[10,11,12] nucleotide binding leucine rich repeat containing proteins (NLRs),[13,14] and the PRR cGAS.[15,16]