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- Title
Mycobacterium tuberculosis lipoprotein-induced association of TLR2 with protein kinase C ζ in lipid rafts contributes to reactive oxygen species-dependent inflammatory signalling in macrophages.
- Authors
Dong-Min Shin; Chul-Su Yang; Ji-Yeon Lee; Sung Joong Lee; Hong-Hee Choi; Hye-Mi Lee; Jae-Min Yuk; Harding, Clifford V.; Eun-Kyeong Jo
- Abstract
Membrane lipid rafts are enriched in cholesterol and play an important role as signalling platforms. However, the roles of lipid rafts and associated signalling molecules in the innate immune responses to mycobacteria remain unknown. Here we show that stimulation with Mycobacterium tuberculosis 19 kDa lipoprotein, a TLR2/1 agonist, results in translocation of TLR2 to lipid rafts, coalescence of lipid rafts and production of reactive oxygen species (ROS) that drive pro-inflammatory responses. Disruption of lipid raft organization markedly reduced lipoprotein-induced ROS and inflammatory responses. Remarkably, the atypical protein kinase C (PKC) ζ was specifically recruited into detergent-resistant membrane fractions and associated with TLR2. PKCζ activity was critical for lipoprotein-dependent ROS generation, raft coalescence and the pro-inflammatory responses by macrophages. Moreover, lipid raft organization was required for 19 kDa mediated PKCζ activation. These results demonstrate that TLR2 trafficking and raft coalescence play an essential role for the initiation of lipoprotein-induced innate immune responses via TLR2 and ROS signalling. In addition, PKCζ targets to lipid rafts and may act as a critical adaptor molecule to regulate lipid raft dynamics during TLR2 signalling.
- Subjects
MYCOBACTERIUM tuberculosis; MEMBRANE lipids; MYCOBACTERIUM; IMMUNE response; REACTIVE oxygen species; CHOLESTEROL; LIPOPROTEINS; MACROPHAGES; TUBERCULIN
- Publication
Cellular Microbiology, 2008, Vol 10, Issue 9, p1893
- ISSN
1462-5814
- Publication type
Article
- DOI
10.1111/j.1462-5822.2008.01179.x