Journal
JOURNAL OF LEUKOCYTE BIOLOGY
Volume 100, Issue 5, Pages 927-941Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1189/jlb.2MR0316-117RR
Keywords
innate immunity; inflammation; pattern recognition receptors; macrophages; signal transduction
Categories
Funding
- U.S. National Institutes of Health [R01AI076588, R01AI076588S1, R03AI097671, R01AI059524]
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TLRs play a critical role in the detection of microbes and endogenous alarmins to initiate host defense, yet they can also contribute to the development and progression of inflammatory and autoimmune diseases. To avoid pathogenic inflammation, TLR signaling is subject to multilayer regulatory control mechanisms, including cooperation with coreceptors, post-translational modifications, cleavage, cellular trafficking, and interactions with negative regulators. Nucleic acid-sensing TLRs are particularly interesting in this regard, as they can both recognize host-derived structures and require internalization of their ligand as a result of intracellular sequestration of the nucleic acid-sensing TLRs. This review summarizes the regulatory mechanisms of TLRs, including regulation of their access to ligands, receptor folding, intracellular trafficking, and post-translational modifications, as well as how altered control mechanism could contribute to inflammatory and autoimmune disorders.
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