Toll-like receptors' pathway disturbances are associated with increased susceptibility to infections in humans.
Toll-like receptors (TLRs) sense microbial products and play an important role in innate immunity. Currently, 11 members of TLRs have been identified in humans, with important function in host defense in early steps of the inflammatory response. TLRs are present in the plasma membrane (TLR1, TLR2, TLR4, TLR5, TLR6) and endosome (TLR3, TLR7, TLR8, TLR9) of leukocytes. TLRs and IL-1R are a family of receptors related to the innate immune response that contain an intracellular domain known as the Toll-IL-1R (TIR) domain that recruits the TIR-containing cytosolic adapters MyD88, TRIF, TIRAP and TRAM. The classical pathway results in the activation of both nuclear factor κB and MAPKs via the IRAK complex, with two active kinases (IRAK-1 and IRAK-4) and two non-catalytic subunits (IRAK-2 and IRAK-3/M). The classical pro-inflammatory TLR signaling pathway leads to the synthesis of inflammatory cytokines and chemokines, such as IL-1β, IL-6, IL-8, IL-12 and TNF-α. In humans, genetic defects have been identified that impair signaling of the TLR pathway and this may result in recurrent pyogenic infections, as well as virus and fungi infections. In this review, we discuss the main mechanisms of microbial recognition and the defects involving TLRs.
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, 1730, Lineu Prestes Avenue, São Paulo, SP, 05508-000, Brazil, britoj@usp.br.
Josias Brito
JB
Frazão
Paolo Ruggero
PR
Errante
Antonio
A
Condino-Neto
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007239:Infections / Q000235:genetics / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology*; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic; D015398:Signal Transduction / Q000235:genetics; D051193:Toll-Like Receptors / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D018836:Inflammation Mediators; D051193:Toll-Like Receptors