Short communication: NKG2C+ NK cells contribute to increases in CD16+CD56- cells in HIV type 1+ individuals with high plasma viral load.

Chronic HIV-1 infection results in the expansion of both NKG2C+ and CD16+CD56- human natural killer cells. NKG2C+ cells proliferate in response to human cytomegalovirus (HCMV) and expansion of the dysfunctional CD56-CD16+ natural killer (NK) cells is associated with HIV-1 viremia. Here we report an association between increased proportions of CD56-CD16+ NK cells in viremic HIV-1+ individuals and an increased contribution of NKG2C+ cells to this subset. These data, in addition to anti-HCMV IgG serology, indicate a potential contribution of both HCMV and HIV-1 to NK cell dysfunction in HIV-1-infected individuals

Elevated plasma lipopolysaccharide is not sufficient to drive natural killer cell activation in HIV-1-infected individuals.

BACKGROUND: Lipopolysaccharide (LPS) is elevated in the plasma of individuals chronically infected with HIV-1 and is thought to contribute to chronic immune activation of myeloid cells and T-cells. Natural killer (NK) cells can also be stimulated by LPS in vitro. OBJECTIVES: To measure plasma LPS levels in individuals with HIV-1 infection, with or without suppressed plasma viral load, and in individuals with or without inflammatory bowel diseases (IBD). To compare the expression of NK cell receptors and activation markers in individuals with HIV-1 infection and in HIV-1-negative individuals with active IBD. METHODS: NK cells were studied by flow cytometry in treatment-naïve viraemic HIV-1-positive individuals (n = 14), aviraemic HIV-1-positive individuals (n = 19), HIV-1-negative individuals with inflammatory bowel disease (n = 10) and HIV-1-negative healthy control individuals (n = 17). Plasma endotoxin (LPS) was measured using the limulus amoebocyte assay. RESULTS: Viraemic and aviraemic HIV-1-positive individuals and patients with IBD have elevated levels of plasma LPS compared with HIV-1-negative individuals.HIV-1-positive individuals had significant changes in activation marker or NK cell receptor expression, whereas NK cells from IBD patients had similar levels to HIV-1-negative controls. NK cells from HIV-1-positive individuals are refractory to further stimulation by LPS in vitro. CONCLUSION: Elevated plasma LPS alone does not account for the chronic activation and receptor loss in NK cells from HIV-1-infected individuals