Heat-shock protein 70 and heat-shock protein 90 associate with Toll-like receptor 4 in response to bacterial lipopolysaccharide.
Mammalian responses to bacterial LPS (lipopolysaccharide) from the outer membrane of Gram-negative bacteria can lead to an uncontrolled inflammatory response that can be deadly for the host. It has been shown that the innate immune system employs at least three cell surface receptors, CD14, TLR4 (Toll-like receptor 4) and MD-2, in order to recognize bacterial LPS. In our previous work we have found that Hsps (heat-shock proteins) are also involved in the innate recognition of bacterial products. Their presence on the cell surface, as well as their involvement in the innate recognition process, are poorly understood. In the present study we have investigated the association of TLR4 with Hsp70 and Hsp90 following LPS stimulation, both on the cell surface and intracellularly. Our results show that Hsp70 and Hsp90 form a cluster with TLR4 within lipid microdomains following LPS stimulation. In addition, Hsp70 and Hsp90 seem to be involved in TLR4/LPS trafficking and targeting to the Golgi apparatus, since upon LPS stimulation we found that both Hsps are targeted to the Golgi along with TLR4. The present study sheds new light into the involvement of Hsps in the innate immune response.
Infection and Immunity Group, University of Sussex, School of Life Sciences, Falmer, Brighton, BN1 9QG, UK.
M
M
Triantafilou
K
K
Triantafilou
D002460:Cell Line; D031541:Fluorescence Resonance Energy Transfer; D006056:Golgi Apparatus / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D018613:Microscopy, Confocal; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors