Immunologic Research

, Volume 34, Issue 1, pp 33–48

New players in TLR-mediated innate immunity

PI3K and small rho GTPases

DOI: 10.1385/IR:34:1:33

Cite this article as:
Ruse, M. & Knaus, U.G. Immunol Res (2006) 34: 33. doi:10.1385/IR:34:1:33


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.

Key Words

Toll-like receptor (TLR) Phosphoinositide 3-kinase Rho GTPase 

Copyright information

© Humana Press Inc 2006

Authors and Affiliations

  1. 1.Dept. of Immunology IMM28The Scripps Research InstituteLa Jolla

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