Deciphering the complexity of Toll-like receptor signaling.
Toll-like receptors (TLRs) are essential players in the innate immune response to invading pathogens. Although extensive research efforts have provided a considerable wealth of information on how TLRs function, substantial gaps in our knowledge still prevent the definition of a complete picture of TLR signaling. However, several recent studies describe additional layers of complexity in the regulation of TLR ligand recognition, adaptor recruitment, posttranslational modifications of signaling proteins, and the newly described, autonomous role of the TLR4 co-receptor CD14. In this review, by using it as model system for the whole TLR family, we attempt to provide a complete description of the signal transduction pathways triggered by TLR4, with a particular emphasis on the molecular and cell biological aspects regulating its function. Finally, we discuss a recently reported model of CD14-dependent signaling and highlight its biological implications.
Ostuni
Renato
R
Department of Biotechnology and Bioscience, University of Milano-Bicocca, Piazza della Scienza 2, 20126, Milan, Italy.
Zanoni
Ivan
I
Granucci
Francesca
F
D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D000818:Animals; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology; D051218:Lymphocyte Antigen 96 / Q000737:chemistry / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*
D033942:Adaptor Proteins, Vesicular Transport; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; D053594:Myeloid Differentiation Factor 88; C470409:TICAM1 protein, human; D051193:Toll-Like Receptors