Evaluation of host genetics on outcome of tuberculosis infection due to differences in killer immunoglobulin-like receptor gene frequencies and haplotypes

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.

Different Selected Mechanisms Attenuated the Inhibitory Interaction of KIR2DL1 with C2+ HLA-C in Two Indigenous Human Populations in Southern Africa

“…In addition, candidates for diseases that could have affected KhoeSan KIR diversity are measles, smallpox and TB, which were introduced to the KhoeSan during the last 250 years by Europeans (102). A case for the role of KIR in NK cell mediated control of TB is being made (103, 104). Supporting this hypothesis, KhoeSan ancestry is associated with increased risk of developing active TB (102), and with the role of activating KIR in preventing that development (105).…”

Activating KIRs alter susceptibility to pulmonary tuberculosis in a South African population

“…As our study indicated that individuals with the aKIR gene 3DS1 and with 5 or more aKIRs, were protected against TB, we show an essential role of aKIRs in TB disease, which could be as a result of altered cytolytic activity of NK cells to M. tuberculosis infected cells. Previous studies have identified associations between KIRs and TB disease outcome [6,8], where NK cells were shown to control M. tuberculosis infection. Individuals with a greater number of aKIRs had a greater NK cell response to mycobacterial infection due to an increased IFN-g response [6] and a lack Table 1 KIR gene profiles and their caseecontrol association data for susceptibility to TB in the SAC population.…”

Clinical and genetic markers associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes

“…Many KIR genes and KIR-HLA-B/KIR-HLA-C pairs have been associated with distinct outcomes in the context of HIV-1 infection [6,[11][12][13][14]. In the same way, genetic studies involving protection or susceptibility to pulmonary tuberculosis have also highlighted the role of HLA-B and KIR genes, as well as KIR + HLA-C pairs [5,[15][16][17][18].…”