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Cell surface molecular chaperones as endogenous modulators of the innate immune response

Martha Triantafilou1, Daniel Sawyer, Abdiaziz Nor

  • 1Infection and Immunity Group, School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, UK.

Novartis Foundation Symposium
|June 26, 2008
PubMed

Insights

Heat shock proteins (HSPs) like Hsp70 and Hsp90 associate with cell surface receptors TLR4/CD14/MD2, regulating innate immune responses to bacterial products. Exogenous Hsp70 inhibits inflammatory signaling and cytokine production.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Mammalian innate immunity recognizes bacterial products via cell surface receptors TLR4, CD14, and MD2.
  • Heat shock proteins (HSPs) are implicated in innate immune recognition, but their cell surface mechanisms are unclear.

Purpose of the Study:

  • To investigate the association of HSPs with the TLR4/CD14/MD2 complex.
  • To elucidate the role of HSPs in regulating innate immune responses to bacterial products.

Main Methods:

  • Investigated the association of Hsp70 and Hsp90 with the TLR4/CD14/MD2 complex on the cell surface.
  • Examined the localization of these associations within lipid rafts.
  • Assessed the effect of exogenous recombinant Hsp70 on inflammatory signaling and cytokine production in vitro.

Main Results:

  • Hsp70 and Hsp90 were found to associate with TLR4 on the cell surface upon stimulation by bacterial products.
  • These associations were observed to occur within lipid rafts.
  • Recombinant Hsp70 demonstrated a dose-dependent inhibition of the inflammatory cascade and cytokine production.

Conclusions:

  • HSPs, specifically Hsp70 and Hsp90, play a role in the innate immune response by associating with TLR4.
  • HSPs may function as endogenous regulators of the innate immune system, modulating inflammatory responses.
  • Lipid rafts are involved in the cell surface complex formation between HSPs and TLR4.

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