NK Cells and immune activation in HIV-1 infection

Natural Killer (NK) cells have the potential to eliminate HIV-1 infected target cells and to influence the rate of HIV-1 disease progression. NK cells are, however, depleted during HIV-1 chronic infection and their functions remain diminished in individuals receiving antiretroviral therapy. Chronic immune activation may contribute to loss of NK cell functional potency in HIV-1 infection.

Aims

Here we investigate the contribution of HIV-1 viraemia and exposure to human cytomegalovirus (HCMV) to chronic NK cell activation and differentiation. We also assess the impact of HIV-1 on NK cells in the gastrointestinal (GI) tract and the association between microbial products translocated from the (GI) tract and chronic activation of NK cells.

Methods

Blood and colonic lamina propria NK cell activation and differentiation were studied in aviraemic and viraemic HIV-1 infected and HIV-1 seronegative control individuals without or with inflammatory bowel diseases (IBD). NK cell activation and receptor expression were assessed by flow cytometry, CMV exposure by anti-HCMV IgG Elisa and plasma lipopolysaccharide (LPS) by limulus amoebocyte assay.

Results

HIV-1 plasma viraemia has a dominant impact on NK cell losses and chronic NK cell activation whereas differentiation of blood NK cell receptor expression is associated with exposure to HCMV in HIV-1+ individuals. HIV-1 plasma viraemia is also associated with depletion of NK cells in the colonic lamina propria whilst atypical gut NK cell differentiation occurs in both HIV-1+ individuals and in HIV-1- IBD patients. Plasma LPS is elevated both in viraemic and aviraemic HIV-1+ individuals and in IBD patients. Chronic NK cell activation is, however, reduced in aviraemic HIV-1+ individuals and is absent in IBD patients.

Discussion

Depletion and chronic activation of NK cells is associated with HIV-1 viraemia whilst concomitant infections and ongoing inflammatory processes influence functional differentiation of NK cells in the blood and GI tract. These data have implications for innate immune competence in HIV-1 infected individuals.