The intracellular replication

and simultaneous dissemination of the pathogen occur prior to the development of the adaptive immune responses. This shows the TGF-beta inhibitor unique feature of M. tb to establish a protected niche where they can avoid elimination by the immune system and persist for ever [4, 5]. The innate immune system has various pathogen recognition receptors (PRRs) that are expressed on the cell surface, in intracellular compartments, or secreted into the blood stream and tissue fluids [6], which specifically recognizes the pathogen-associated molecular patterns (PAMP) for initiating and coordinating the host innate immune response [7]. As per the recent research on PRRs like Toll-like receptors (TLRs), nucleotide oligomerization domain (NOD)-like receptors (NLRs) and other C-type lectin receptors plays an important role in the recognition of M. tb. Here, we have summarized the information available on host innate immune response especially TLRs, host–pathogen interaction and the

importance of signal transduction mechanisms involved in the pathogenesis of TB. TLRs are phylogenetically conserved mediators of innate immunity, which are essential for microbial recognition on macrophages and DCs [8-10]. Toll was first identified in Drosophila as a type I transmembrane receptor, which controls dorsal–ventral Trametinib manufacturer polarity during embryogenesis [11]. After the identification of Toll as an essential receptor in the innate immune

recognition in Drosophila, a homology search of databases lead to the discovery of a homologue of Toll in humans [9]. It is now designated as TLR4 and is involved in the gene expression of inflammatory cytokines and costimulatory molecules [9]. Later studies identified several proteins that are structurally related to TLR4. Currently, 11 mammalian TLRs Tacrolimus (FK506) were identified of which TLR1-10 are functional in humans. TLRs are transmembrane proteins containing lucine-rich repeats (LRR) in their extracellular domains. The cytoplasmic domain of TLR is homologous to the signalling domain of Interleukin-1 receptor (IL-1R) known as Toll/IL-1 (TIR) domain that links to IL-1R-associated kinase (IRAK), a serine kinase that activates transcription factors like nuclear transcription factor (NF)-κB, which leads to the production of cytokines. Activation of TLR by its specific ligand may result in several possible biological outcomes, ranging from the cytokine secretion, modulation of the adaptive immune response, rapid cellular differentiation, apoptosis and direct antimicrobial activity [12-14]. Of 10 TLRs, TLR1, TLR2, TLR4, TLR6, TLR8 and TLR9 are thought to be involved in the recognition of mycobacteria. Most important M. tb cell-surface ligands that interact with TLRs and other receptors are 19- and 27-kDa lipoproteins, 38-kDa glycolipoprotein, the lipomannan (LM) and mannose-capped lipoarabinomannan (ManLAM) [15-17].