The role of TLR9 polymorphism in susceptibility to pulmonary tuberculosis

Deepak Bharti, Ashish Kumar, Ranjeet Singh Mahla, Sushil Kumar, Harshad Ingle, Hari Shankar, Beenu Joshi, Ashwin Ashok Raut, Himanshu Kumar

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


Mycobacterium tuberculosis (MTB) is the causative agent of pulmonary tuberculosis (PTB), a major health problem that leads to 1.5 million deaths annually. Host genetic factors play a significant role in disease resistance/susceptibility by altering immunity against MTB. Toll-like receptor (TLR) sensors such as TLR2, TLR4, TLR8, and TLR9 are known to play a pivotal role in PTB via modulating sensor expression and/or effector responses. Single-nucleotide polymorphism (SNP) rs187084 (T-1486C) of the TLR9 promoter is associated with various autoimmune disorders and cancers. A recent bioinformatic analysis predicted that the T-1486C SNP is involved in PTB, although its potential role is unclear. To investigate the role of T-1486C in PTB, we stimulated PBMCs with the H37Rv whole cell lysate. We found that the presence of the “C” allele increases the transcriptional activity of the TLR9, which in turn induces high levels of Interferon gamma-induced protein 10 (IP-10), a biomarker for PTB. However, the expression of protective cytokines such as IFNγ and TNFα was observed significantly less with “C” allele in comparison to “T” allele. We further selected three different tribe populations showing differential susceptibility to PTB and performed genotypic analyses for the TLR9 promoter. We found a significantly lower minor allele frequency (MAF) of T-1486C in the Baiga tribe, wherein fewer PTB cases were reported, than that in the Gond and Korku tribes. Collectively, these data suggest that the minor “C” allele at rs187084 locus may be associated with susceptibility to PTB, which may explain the relatively lower PTB rates observed in Baiga tribe members.

Original languageEnglish
Pages (from-to)675-681
Number of pages7
Issue number12
StatePublished - Nov 8 2014


  • IFNγ
  • IP-10
  • Pulmonary tuberculosis (PTB)
  • Single-nucleotide polymorphism (SNP)
  • TNFα
  • Tribes


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