Open AccessLipopolysaccharides from atherosclerosis‐associated bacteria antagonize TLR4, induce formation of TLR2/1/CD36 complexes in lipid rafts and trigger TLR2‐induced inflammatory responses in human vascular endothelial cells
Author(s) -
Triantafilou Martha,
Gamper Frederick G. J.,
Lepper Philipp M.,
Mouratis Marios Angelos,
Schumann Christian,
Harokopakis Evlambia,
Schifferle Robert E.,
Hajishengallis George,
Triantafilou Kathy
Publication year - 2007
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2007.00935.x
Subject(s) - tlr2 , innate immune system , tlr4 , biology , pattern recognition receptor , porphyromonas gingivalis , cd36 , toll like receptor , lipopolysaccharide , lipid raft , microbiology and biotechnology , immunology , receptor , inflammation , immune system , signal transduction , bacteria , biochemistry , genetics
Summary Infection with bacteria such as Chlamydia pneumonia , Helicobacter pylori or Porphyromonas gingivalis may be triggering the secretion of inflammatory cytokines that leads to atherogenesis. The mechanisms by which the innate immune recognition of these pathogens could lead to atherosclerosis remain unclear. In this study, using human vascular endothelial cells or HEK‐293 cells engineered to express pattern‐recognition receptors (PRRs), we set out to determine Toll‐like receptors (TLRs) and functionally associated PRRs involved in the innate recognition of and response to lipopolysaccharide (LPS) from H. pylori or P. gingivalis . Using siRNA interference or recombinant expression of cooperating PRRs, we show that H. pylori and P. gingivalis LPS‐induced cell activation is mediated through TLR2. Human vascular endothelial cell activation was found to be lipid raft‐dependent and to require the formation of heterotypic receptor complexes comprising of TLR2, TLR1, CD36 and CD11b/CD18. In addition, we report that LPS from these bacterial strains are able to antagonize TLR4. This antagonistic activity of H. pylori or P. gingivalis LPS, as well as their TLR2 activation capability may be associated with their ability to contribute to atherosclerosis.