Natural killer cell-mediated cytokine response among HIV-positive south Indians with pulmonary tuberculosis

Abstract

Natural killer (NK) cells control Mycobacterium tuberculosis infection mainly through secreted cytokines. Cytokine dysregulation among HIV may cause rapid disease progression. Our objective was to examine whether impaired production of innate cytokines are responsible for cytokine dysregulation during HIV infection. The study included 30 subjects each of normal healthy subjects (NHS), pulmonary tuberculosis patients (TB), HIV-infected individuals (HIV), and HIV-TB co-infected patients (HIV-TB). Intracellular cytokine staining method was used to enumerate the cytokine-positive NK cells. Unlike NHS (100%), only 27% of HIV-TB and 57% of HIV infected patients have detectable plasma interleukin (IL)-15 levels that signify impaired rather than decreased IL-15 production. Basal type 1 cytokine (IL-2, interferon-gamma [IFN-gamma], and tumor necrosis factor-alpha [TNF-alpha])-secreting NK cells (NK1 cytokines) were decreased significantly (P < 0.05) in TB, HIV, and HIV-TB, when compared with NHS. Stimulation with M. tuberculosis H37Rv enhanced the NK1 cytokines in NHS (P < 0.05), but not in other groups. With IL-15+IL-12 stimulation, we found increased NK1 cytokines (IL-2 and IFN-gamma) in HIV (P < 0.05), but not in HIV-TB, when compared to unstimulated condition. Supplementing IL-15+IL-12 has potential in improving the frequency of NK1 cytokines for HIV, but not HIV-TB, suggesting that TB influences cytokine response during HIV infection.