Human Integrin α3β1 Regulates TLR2 Recognition of Lipopeptides from Endosomal Compartments
| العنوان: | Human Integrin α3β1 Regulates TLR2 Recognition of Lipopeptides from Endosomal Compartments |
|---|---|
| المؤلفون: | Courtney T. Darcy, Alicia S. DeFrancesco, Linden T. Hu, Meghan L. Marre, Tanja Petnicki-Ocwieja |
| المصدر: | PLoS ONE, Vol 5, Iss 9, p e12871 (2010) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Endosome, Immunology/Innate Immunity, Integrin, lcsh:Medicine, Microbiology/Innate Immunity, Endosomes, Endocytosis, Lipopeptides, 03 medical and health sciences, 0302 clinical medicine, Immunology/Immunity to Infections, Humans, Secretion, lcsh:Science, 030304 developmental biology, Lyme Disease, 0303 health sciences, Multidisciplinary, biology, Macrophages, lcsh:R, Integrin alpha3beta1, Toll-Like Receptor 2, Microbiology/Immunity to Infections, 3. Good health, Cell biology, TLR2, Borrelia burgdorferi, Immunology/Immune Response, biology.protein, lcsh:Q, Integrin, beta 6, Signal transduction, Signal Transduction, Research Article, 030215 immunology |
| الوصف: | Background: Toll-like receptor (TLR)-2/TLR1 heterodimers recognize bacterial lipopeptides and initiate the production of inflammatory mediators. Adaptors and co-receptors that mediate this process, as well as the mechanisms by which these adaptors and co-receptors function, are still being discovered. Methodology/Principal Findings: Using shRNA, blocking antibodies, and fluorescent microscopy, we show that U937 macrophage responses to the TLR2/1 ligand, Pam3CSK4, are dependent upon an integrin, a3b1. The mechanism for integrin a3b1 involvement in TLR2/1 signaling is through its role in endocytosis of lipopeptides. Using inhibitors of endosomal acidification/maturation and physical tethering of the ligand, we show that the endocytosis of Pam3CSK4 is necessary for the complete TLR2/1-mediated pro-inflammatory cytokine response. We also show that TLR2/1 signaling from the endosome results in the induction of different inflammatory mediators than TLR2/1 signaling from the plasma membrane. Conclusion/Significance: Here we identify integrin a3b1 as a novel regulator for the recognition of bacterial lipopeptides. We demonstrate that induction of a specific subset of cytokines is dependent upon integrin a3b1-mediated endocytosis of the ligand. In addition, we address an ongoing controversy regarding endosomal recognition of bacterial lipopeptides by demonstrating that TLR2/1 signals from within endosomal compartments as well as the plasma membrane, and that downstream responses may differ depending upon receptor localization. We propose that the regulation of endosomal TLR2/1 signaling by integrin a3b1 serves as a mechanism for modulating inflammatory responses. |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6d3d823bbe0240045b1e0d8bacf51b9f https://doi.org/10.1371/journal.pone.0012871 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....6d3d823bbe0240045b1e0d8bacf51b9f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
|---|