A

study reported that 745T and 1083C were associated with increased IFN-γ or IL-2 levels after BCG vaccination [84], but the mechanism is still unclear (Table 1). TLR8 is located on X chromosome and able to recognize single-stranded RNA from pathogens such as RNA viruses. According to the literature, Davila et al. [85] first reported TLR8 SNPs, and they have analysed 149 SNPs from Indonesian and Russian pulmonary TB patients, of these four SNPs were significantly associated with the pulmonary TB among Indonesian and Russian males. Three of the associated TLR8 variants are −129 C/G, −2167 A/G and −1145 A/G present in the regulatory regions, and one variant 1 A/G (Met1Val) at the start codon. Indonesian males were carriers of Met1Val, allele A showed an increased susceptibility to pulmonary TB, While G allele shows protection from TB. Another study reported in Dinaciclib Turkish children [86] also showed an association with susceptibility to pulmonary TB among male children, but found no associations with −129 C/G SNP for TB susceptibility in children, whereas Davila et al. found a strong allelic association with minor allele C in susceptibility to pulmonary TB in males, but the mechanism through which

TLR8 recognizes M. tb and intracellular signalling remains unknown (Table 1). TLR9 composed of 2 exons and encodes 1032 amino acids [87]. It recognizes unmethylated CpG motifs in bacterial DNA. It Ferroptosis inhibitor drugs was found to be essential for cellular responses to mycobacterial CpG DNA [88]. In vitro studies showed that DCs release IL-12 in response to M. tb through TLR9 [89, 90]. A report demonstrates that TLR9-deficient mice are susceptible to Mtb infection, and mice lacking both TLR2 and TLR9 are more susceptible [89] to TB. Four SNPs, C-1486T, C-1237T, G+1174A and G+2848A, have been reported to show high heterozygocity among three major US ethnic groups [91]. C-1237T, a polymorphism Endonuclease located within the putative promoter region that may influence transcriptional regulation of the TLR9 gene.

SNP G+1174A, located in the intron of TLR9, showed a significant association with TB in Indonesian females [92]. Promoter polymorphisms, namely −1237C/T and −1486C/T, are not associated with pulmonary TB in south Indian population [93]. TLR9 activation is essential for the maintenance of M. tb Ag elicited pulmonary granulomatous response; however, the underlying mechanism is not known. SNPs in promoter region potentially affect gene expression levels by altering the binding of gene transcription factors and SNPs in introns, affecting mRNA splicing and/or enhancement of gene transcription. Carvalho et al. [94] reported that peripheral blood mononuclear cells (PBMCs) harbouring the -1237 TC genotype shown higher expression of both TLR9 and IL-6 and increased B-cell proliferation in response to CpG DNA, but the mechanism is not known (Table 1).