Phenotypic and functional evaluation of NK Cells in men who have sex with men at high risk of HIV-1 infection from Medellin

Abstract

ABSTRACT: Introduction: HIV exposed seronegative (HESN), are individuals that remain seronegative despite repeated exposure to HIV. Since the first reports of HIV resistance in humans in 1989, HESN individuals turn in to a key population for the research of the phenomenon of human natural resistance to HIV-1. Studies conducted in this population allowed to describe different immunological and genetic mechanisms associated with viral resistance. A higher effector capacity of NK cells has been related to natural resistance in different HESN cohorts. Besides, recently a population of NK cells with memory features has been described; these cells are increased in HESN individuals and they are involved in better control of HIV replication in primarily HIV infected subjects. Although men who have sex with men (MSM) are one of the main cohorts for the study of HESN, this population has been poorly studied compared to others like commercial sex workers (CSW) and intravenous drug users (UDI). However, some mechanisms of natural resistance have been described in them. The role of NK cells on HIV resistance has not been studied in this population so far. This study evaluates the role of NK cells in the natural resistance to HIV-1 infection in MSM. Methodology: Phenotypic and functional features were evaluated in NK cells from two groups of MSM, at different risk of HIV infection defined based on the number of sexual partners. Production of IFN-γ and β-chemokines were included in the analysis as well as the cytotoxic capacity and memory markers. Genetic features such as HLA and KIR alleles were also explored. Results: High-risk MSM showed an increased frequency of fully mature NK cells (CD56dimCD57+) as well as memory NK cells (CD56dimCD57+NKG2Chigh). High-risk MSM also show higher cytotoxic capacity and IFN-γ production against K562 stimuli. A subpopulation of NK cells with CD107a+/IFN-ɣ+/MIP-1β- functional profile was found in higher frequency among high-risk MSM compared to low-risk MSM. This NK cells population displays higher MFI of IFN-γ in MSM at high risk compared to low risk, characteristic absent in NK cells with other functional profiles. Protective KIR/HLA phenotype KIR3DL1/S1-HLA-B*Bw4 in a homozygous state was found in 30.7% of High-risk MSM. Of note, some of these functional features were related to higher frequencies of mature and memory NK cells, which in turn, were associated with the higher number of sexual partners found in high-risk MSM. Conclusion: The changes observed in NK cells compartment can be driven by the magnitude of sexual exposure and immunological challenges of high-risk individuals, that could influence their resistance/susceptibility to HIV infection.