Ten functional TLR members (TLR1�CTLR13) have been identified in humans. selleck products TLR4 is activated by bacterial lipopolysaccharides (LPSs) and has critical role in initiation of innate immune system [4�C6]. TLR4 has been shown to activate IL-1 receptor-associated kinase in response to a variety of PAMPs, such as Gram-negative enterobacterial LPS [7]. The TLR4 gene is located on chromosome 9q32-33, spans approximately 13kb, and contains three exons that encode a 222-amino acid protein. Several studies show that synergic effect of two variants of TLR4 gene, Asp299Gly (rs4986790) and Thr399Ile (rs4986791) which both are encoded within the fourth exon of the TLR4 gene, are associated with an endotoxin-hyporesponsive phenotype.

Moreover, the Asp299Gly polymorphism is associated with airway hyporesponsiveness in either human primary airway epithelial cells or alveolar macrophages obtained from individuals with these TLR4 mutations [8�C11]. TLR9, an endosomal localized receptor on B cells, plasmacytoid dendritic cells (pDCs), and monocytes/macrophages, recognizes unmethylated nucleic acid motifs, especially Cytosine-phosphate-Guanine (CpG) motifs, in bacterial DNA [12], and it is one of the most important receptors in the initiation of protective immunity against intracellular pathogens by activation signaling cascade of intracellular receptor signaling [13, 14]. TLR9 encoding gene is located on chromosome 3p21.3. It spans approximately 5kb and contains two exons, the second of which is the major coding region [12�C14].

Twenty SNPs have been identified for TLR9, which -1486T/C (rs187084) in the promoter region in intron 1 is one of the most important SNPs [15, 16]. TLR4 and TLR9 gene polymorphisms have been extensively studied for their association with susceptibility or resistance Drug_discovery to many infections and diseases [17�C22]. Therefore, the association between progress and severity of infectious diseases with TLR4 [23�C27] and TLR9 [28, 29] gene polymorphisms has been confirmed. It has been shown that TLR4 and TLR9 have critical roles in the recognition of MT, and they are necessary for development of an adequate immune response against MT [30�C33]. TLR-knockout mouse studies indicate that TLR4 and TLR9 contribute to host resistance to M. tuberculosis infection [34]. Moreover, associations between genetic variations of TLR4 and TLR9 and TB have been reported [35�C42]. There have been no reports about the association of TLR4 and TLR9 with TB in Iran so far. The aim of the present study was to investigate the potential association between pulmonary TB, a TB infection of the lungs, and three SNPs in TLR4 and TLR9 genes in southeastern Iranian population, Zahedan.2. Materials and Methods2.1.