The Toll-like Receptor Family

Toll-like receptors (TLRs) comprise a major family of pattern-recognition receptors (PRRs) that fulfill a key role in recognizing, discriminating and responding appropriately to microbial infection. Although expressed principally by macrophages and dendritic cells, TLRs expression is widespread and includes, but is not limited to cells of myeloid and lymphoid origin. Activation of TLRs by their cognate ligands can lead to induction of proinflammatory cytokine and antimicrobial peptide expression or up regulation of type 1 interferons. Whilst central to innate immunity, TLRs can additionally communicate with the adaptive immune response via modulation of cell-adhesion and co-stimulatory molecules to induce longer term immunity. Interestingly a selection of non-microbial endogenous factors can also activate certain TLRs, with dysregulation of these events having potentially deleterious consequences. Since the first report of human TLR4 by Medzhitov and Janeway in 1997 [1] there has been huge progress in elucidating the fundamental processes controlling the biology of the TLR family.

Keywords: TLRs, PAMPs, DAMPs, MyD88-dependent, TRIF-dependent signaling.