Antigen-presenting phagocytic cells ingest malaria parasites and increase hiv replication in a tumor necrosis factor α-dependent manner

Abstract

Background.Plasmodium falciparum infection induces human immunodeficiency virus (HIV) replication and accelerates a decline in CD4+ T-cell count. The mechanisms contributing to these interactions have not been fully elucidated. Methods.We infected peripheral blood mononuclear cells (PBMCs) with HIV type 1 (HIV-1) and then cocultured them with P. falciparum-infected red blood cells (iRBCs) or uninfected RBCs (uRBCs). Levels of HIV-1 p24 antigen and activation-associated cytokines were measured in culture supernatants. T-cell surface activation was assessed by flow cytometry. Results.It has been reported that iRBCs increase HIV replication, compared with uRBCs; that neutralizing tumor necrosis factor α (TNF-α) abrogates this increase; and that hemozoin enhances HIV production. In this study, we confirmed that TNF-α plays an important role in this interaction. We show that iRBCs increased CD4+ T-cell expression of HLA-DR+/CD38+ (P =. 001), that monocyte/macrophage depletion reduced HIV production by 40%-50% (P