P2X Antagonists Inhibit HIV-1 Productive Infection and Inflammatory Cytokines Interleukin-10 (IL-10) and IL-1β in a Human Tonsil Explant Model.

摘要: HIV-1 causes a persistent infection of the immune system that is associated with chronic comorbidities. The mechanisms underlie this inflammation are poorly understood. Emerging literature has implicated proinflammatory purinergic receptors and downstream signaling mediators in infection. This study probed whether inhibitors would reduce HIV-1-stimulated inflammation. An ex vivo human tonsil histoculture model was developed to support productive stimulated inflammatory cytokine interleukin-1 beta (IL-1β) immunosuppressive interleukin-10 (IL-10). tests P2X1 receptor antagonist NF449, P2X7 A438079, azidothymidine (AZT) were tested HIV-1-infected explants compare levels inhibition HIV-stimulated production. All drugs limited infection, but P2X-selective antagonists (NF449 A438079) significantly lowered IL-10 IL-1β. We further observed P2X1- P2X7-selective can act differentially as both Our findings highlight differential effects on peripheral blood compared those lymphoid tissue. For first time, we demonstrate Drugs block these pathways have independent inhibitory activities against HIV-induced inflammation.IMPORTANCE Patients who chronically infected experience sequelae related not been elucidated. Here, describe class target P2X explant model. highlights differences stimulation tissue blood. These serve production IL-1β tissue, suggesting novel approach therapeutics which replication simultaneously targeted.