Toll-like receptors and the host defense against microbial pathogens: bringing specificity to the innate-immune system

Toll-like receptors (TLRs) have been identified as a major class of pattern-recognition receptors. Recognition of pathogen-associated molecular patterns (PAMPs) by TLRs, alone or in heterodimerization with other TLR or non-TLR receptors, induces signals responsible for the activation of genes important for an effective host defense, especially proinflammatory cytokines. Although a certain degree of redundancy exists between signals induced by the various TLRs, recent studies have identified intracellular pathways specific for individual TLRs. This leads to the release of cytokine profiles specific for particular PAMPs, and thus, TLRs confer a certain degree of specificity to the innate-immune response. In addition to the activation of the innate-immune response, TLR-mediated recognition represents a link between the innate- and acquired-immune systems, by inducing the maturation of dendritic cells and directing the T helper responses. Alternatively, recent data have also suggested TLR-mediated escape mechanisms used by certain pathogenic microorganisms, especially through TLR2 induction of anti-inflammatory cytokines. Finally, the crucial role of TLRs for the host defense against infections has been strengthened recently by the description of patients partially defective in the TLR-activation pathways.