Toll-like receptors and control of mammalian immunity

Abstract

Toll-like receptors (TLRs) is a family of pattern-recognition receptors that detects conserved pathogen-associated molecular patterns (PAMPs)—a product produced uniquely by microorganisms but not by the host organisms. TLRs function as crucial sensors of microbial infection. Upon recognition of microbial products, TLRs induce signaling pathways that initiate the inflammatory and immune responses. The signaling pathways activated by individual TLRs are complex and it is becoming evident that different TLRs can trigger differential signaling, which translates into induction of the immune responses tailored to the nature of the infectious agent. In addition to directly triggering the innate host defense responses, TLR-mediated recognition and signaling plays a crucial role in the control of initiation of the adaptive immune responses. While the details of the mechanisms responsible for these controls are only starting to emerge, there appears to be at least two distinct pathways of TLR-mediated control of T cell activation. One has to do with the co-stimulatory pathway, and the other with the cytokine-dependent block of suppressor activity of regulatory T cells (Tr cells). TLR-induced cytokines, in particular IL-6, render pathogen specific T cells refractory to the suppressive effect of Tr cells, thus allowing the initiation of the protective pathogen-specific T cell responses.