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New players in TLR-mediated innate immunity

PI3K and small rho GTPases

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An Erratum to this article was published on 01 March 2006

Abstract

Toll-like receptors (TLRs) play a crucial role in the innate immune system as a first line of defense against pathogens. TLR activation in phagocytes produces pro-inflammatory cytokines and chemokines that contribute directly to elimination of infectious agents and activation of adaptive immune responses. However, a sustained inflammatory response can result in tissue damage and generalized sepsis. This review summarizes the complex and sometimes conflicting links of TLR signaling with two important regulators of immune cells functions: phosphoinositide 3-kinases (PI3Ks) and small GTPases of the Rho family. A unified model of hierarchical organization of these signaling participants is still premature, given that the tools for delineating how control of TLR-mediated pathways is achieved are just emerging. Critical progress in our understanding of spatial-temporal propagation of TLR signaling will certainly be provided in the near future by pharmacological targeting of PI3Ks using recently characterized, second-generation PI3K inhibitors in combination with gene-targeting strategies for PI3K subunits and Rho GTPases targeted to the murine myeloid compartment.

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  1. Dept. of Immunology IMM28, The Scripps Research Institute, 10550 North Torrey Pines Rd., 92037, La Jolla, CA

    Monica Ruse & Ulla G. Knaus

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  1. Monica Ruse
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  2. Ulla G. Knaus
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Correspondence to Ulla G. Knaus.

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An erratum to this article is available at http://dx.doi.org/10.1385/IR:34:3:255.

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Ruse, M., Knaus, U.G. New players in TLR-mediated innate immunity. Immunol Res 34, 33–48 (2006). https://doi.org/10.1385/IR:34:1:33

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