Toll-like receptor 2 (TLR2) is a member of the Toll-like receptor (TLR) family, which plays a role in activation of innate immunity and pathogen recognition []. It helps mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components, acting via MyD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response [, , , ]. TLR2 in association with TLR1 or TLR6 is essential for recognising bacterial lipoproteins and lipopeptides [, ]. It also promotes apoptosis in response to lipoproteins [].Genetic variations in TLR2 are associated with susceptibility to leprosy, a chronic disease associated with depressed cellular (but not humoral) immunity [, ].
Toll-like receptor 1 (TLR1) participates in the innate immune response to microbial agents. TLR1 cooperates with TLR2 to mediate the innate immune response to bacterial lipoproteins or lipopeptides [, ]. It acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.
Tollip (Toll-interacting protein) is a component of the IL-1RI pathway which contains an N-terminal C2 domain and a C-terminal CUE domain. Tollip binds to the cytoplasmic TIR domain of IL-1Rs after IL-1 stimulation. It is sufficient for recruitment of IRAK to IL-1Rs and negatively regulates IL-1-induced signaling by inhibiting IRAK phosphorylation. In addition, Tollip directly interacts with toll-like receptors TLR2 and TLR4, and plays an inhibitory role in TLR-mediated cell activation through suppressing phosphorylation and kinase activity of IRAK. Moreover, Tollip can associate with GAT domains of Tom1 and its related proteins Tom1L1 and Tom1L2, and facilitate the recruitment of clathrin onto endosomes [, ].
Toll-like receptor 6 (TLR6) participates in the innate immune response to Gram-positive bacteria and fungi. TLRs recognize specific molecular patterns present only in micro-organisms. TLR1 and TLR6 are involved in the discrimination of a subtle difference between triacyl and diacyl lipopeptides through interaction with TLR2 []. Cooperatively with TLR2, TLR6 recognises mycoplasmal macrophage-activating lipopeptide-2 (MALP-2), soluble tuberculosis factor (STF), phenol-soluble modulin (PSM) and Borrelia burgdorferi outer surface protein A lipoprotein (OspA-L) []. TLR6 acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response [].
C-type lectin domain family 7 member A (CLEC7A), also known as Dectin-1, is a beta-glucan receptor that binds beta-1,3 and beta-1,6 glucans and collaborates with with TLR2 to activate a macrophage's proinflammatory response to a mycobacterial infection []. It is a type II transmembrane protein of the C-type lectin family with single carbohydrate recognition domains (CRDs) in their extracellular region []. Its cytoplasmic tail contains an immunoreceptor tyrosine based activation motif (ITAM) that signals in part through the spleen tyrosine kinase and in collaboration with Toll-like receptors. It plays an important role in the host defense against fungal infection [, ].
This entry consists of several lipoproteins mainly from Mycobacterium species, collectively known as the LppX/LprAFG family. Proteins in this entry include:LprG () from Mycobacterium tuberculosis: an immunogenic 27kDa membrane-associated lipoprotein []. Expression of the LprG protein is essential for the growth of M. tuberculosis in immunocompetent mice []. Purification of LprG showed that it inhibits MHC-II antigen processing in primary human macrophages, providing a mechanism to avoid the host MHC-II-restricted CD4+ T cell response which is considered essential for control of M. tuberculosis infection []. LppX: a lipoprotein required for the translocation of complex lipids to the outer membrane of Mycobacterium tuberculosis. Its structure consists of a U-shaped β-half-barrel with a large hydrophobic cavity []. LprF: a membrane lipoprotein involved in the kdp signal transduction pathway, thought to be the primary response to osmotic stress [].lprA: a lipoprotein agonist of TLR2 that regulates innate immunity and APC function [].
