Abstract
BackgroundOutcome of Mycobacterium tuberculosis (Mtb) infection is affected by virulence of the infecting strain of Mtb, host environment, co-morbidities, and the genetic composition of the host, specifically the presence or absence of genes involved in immune responses/regulation. It is hypothesized that specific killer immunoglobulin-like receptor (KIR) genes may be associated with Mtb infection and clinical outcome. This cross-sectional study examined the KIR gene frequencies, profiles, and haplotypes of individuals with active tuberculosis, latent tuberculosis infection, compared to TB and HIV negative healthy controls.ResultsAnalysis of KIR gene frequencies revealed differences among disease status groups, suggesting that enrichment or depletion of specific KIR genes may direct the disease outcome. Mtb infected individuals were more likely to have a centromeric-AA haplotype compared to controls.ConclusionThe differences in KIR gene frequencies and haplotypes may result in differential cytokine expression, contributing to different disease outcomes, and suggest a genetic influence on Mtb susceptibility and pathogenesis.
Highlights
Outcome of Mycobacterium tuberculosis (Mtb) infection is affected by virulence of the infecting strain of Mtb, host environment, co-morbidities, and the genetic composition of the host, the presence or absence of genes involved in immune responses/regulation
killer immunoglobulin-like receptor (KIR) gene frequencies In order to determine the differences in KIR gene frequencies between different disease status groups (ATB, latent TB infection (LTBI), and controls), the KIR gene frequency data obtained was analyzed and compared
Two genes differed between individuals with Mtb infection (LTBI and active TB (ATB)) vs. controls, KIR2DL2 (33.33 % vs. 55.77 %, P = 0.0014) and KIR2DS2 (34.29 % vs. 54.81 %, P = 0.0035)
Summary
Outcome of Mycobacterium tuberculosis (Mtb) infection is affected by virulence of the infecting strain of Mtb, host environment, co-morbidities, and the genetic composition of the host, the presence or absence of genes involved in immune responses/regulation. It is hypothesized that specific killer immunoglobulin-like receptor (KIR) genes may be associated with Mtb infection and clinical outcome. This cross-sectional study examined the KIR gene frequencies, profiles, and haplotypes of individuals with active tuberculosis, latent tuberculosis infection, compared to TB and HIV negative healthy controls. The incidence of TB in Manitoba was more than twice the national rate at 138 cases (10.9/100,000). The immune response to an intracellular pathogen such as Mycobacterium tuberculosis (Mtb) involves natural killer (NK) cells to bridge the innate and adaptive immune response to infection [3].
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