Deepak Bharti’s research while affiliated with Indian Institute of Science Education and Research, Bhopal and other places

Human immunodeficiency virus-1 (HIV-1) which causes acquired immune deficiency syndrome (AIDS), by infecting CD4+ immune cells and hence weakening the host defense mechanism till death, is one of the major factor responsible for human demises worldwide. Both innate (monocytes and macrophages) and adaptive (T cells) immune cells expresses chemokines receptors (2 and 5) and stromal cell derived factor-1 (SDF-1) which play crucial role in HIV-1 virus entry and progression. Allele variants of genes CCR5 (CCR5-Δ32), CCR2 (CCR2-64I) and SDF1 (SDFA-3′A; the ligand of CXCR4) are known to slow down the HIV-1 progression in infected individual. In the present study, the frequency of CCR5-Δ32, CCR2-64I and SDF1-3′A alleles in primitive tribe (Baiga) and a non-primitive tribe (Gond) of central India were investigated. A total 200 seronegative samples for HIV from healthy individuals of tribes were analyzed and observed allele frequencies of CCR5-Δ32, CCR2-64I and SDF1-3′A were (0, 0.035, 0.080) and (0, 0.110, 0.100) in Baiga and Gond respectively. Minor allele frequency of these alleles of Gond and Baiga tribes were compared with different populations of the world for relative hazard (RH), which indicate the risk of progression after infection of HIV1. The RH values were calculated based on genotypic frequency, showed the high RH value (RH1-AIDS1993-0.98, RH2-AIDS1987-0.98 and death/RH3-0.97) in Baiga tribe, indicates the low level of resistance against HIV-1 progression after infection. Electronic supplementary material The online version of this article (doi:10.1186/s40064-015-1238-6) contains supplementary material, which is available to authorized users.

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.