Journal
JOURNAL OF LEUKOCYTE BIOLOGY
Volume 106, Issue 1, Pages 147-160Publisher
WILEY
DOI: 10.1002/JLB.3MIR1218-483RR
Keywords
innate immunity; autoimmunity; intracellular signaling; receptors trafficking; inflammation
Categories
Funding
- NIH [1R01AI121066-01A1]
- Harvard Medical School Milton Fund
- CCFA Senior Research Awards
- Cariplo Foundation
- Associazione Italiana per la Ricerca sul Cancro [IG 2016Id.18842]
- Cariplo Foundation [2014-0655]
- Fondazione Regionale per la Ricerca Biomedica, FRRB
- [HDDC P30 DK034854]
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TLRs are a class of pattern recognition receptors (PRRs) that detect invading microbes by recognizing pathogen-associated molecular patterns (PAMPs). Upon PAMP engagement, TLRs activate a signaling cascade that leads to the production of inflammatory mediators. The localization of TLRs, either on the plasma membrane or in the endolysosomal compartment, has been considered to be a fundamental aspect to determine to which ligands the receptors bind, and which transduction pathways are induced. However, new observations have challenged this view by identifying complex trafficking events that occur upon TLR-ligand binding. These findings have highlighted the central role that endocytosis and receptor trafficking play in the regulation of the innate immune response. Here, we review the TLR4 and TLR9 transduction pathways and the importance of their different subcellular localization during the inflammatory response. Finally, we discuss the implications of TLR9 subcellular localization in autoimmunity.
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