Neutrophils in antiretroviral therapy-controlled HIV demonstrate hyperactivation associated with a specific IL-17/IL-22 environment.

BACKGROUND: Despite control of HIV infection under antiretroviral therapy (ART), immune T-cell activation persists in patients with controlled HIV infection, who are at higher risk of inflammatory diseases than the general population. PMNs play a key role in host defenses against invading microorganisms but also potentiate inflammatory reactions in cases of excessive or misdirected responses. OBJECTIVE: The aim of our study was to analyze PMN functions in 60 ART-treated and controlled HIV-infected patients (viral load, <20 RNA copies/mL; CD4 count, ≥ 350 cells/mm(3)) with (HIV[I] group) and without (HIV[NI] group) diseases related to an inflammatory process and to compare them with 22 healthy control subjects. METHODS: Flow cytometry was used to evaluate PMN functions in whole-blood conditions. We studied in parallel the activation markers of T lymphocytes and monocytes and the proinflammatory cytokine environment. RESULTS: Blood samples from HIV-infected patients revealed basal PMN hyperactivation associated with deregulation of the apoptosis/necrosis equilibrium. Interestingly, this hyperactivation was greater in HIV(I) than HIV(NI) patients and contrasted with a lack of monocyte activation in both groups. The percentage of circulating cells producing IL-17 was also significantly higher in HIV-infected patients than in control subjects and was positively correlated with markers of basal PMN activation. In addition, the detection of IL-22 overproduction in HIV(NI) patients suggests that it might contribute to counteracting chronic inflammatory processes during HIV infection. CONCLUSIONS: This study thus demonstrates the presence of highly activated PMNs in HIV-infected patients receiving effective ART and the association of these cells with a specific IL-17/IL-22 environment.