Impaired Complement-Mediated Phagocytosis by HIV Type-1-Infected Human Monocyte-Derived Macrophages Involves a cAMP-Dependent Mechanism

HIV-1 infection of cells of macrophage lineage impairs a number of effector functions performed by these cells, including phagocytosis of opsonized pathogens. In this study we investigate the effects of HIV-1 on the mechanism of complement (C′)-mediated phagocytosis by human monocyte-derived macrophages (MDM). Using C′-opsonized sheep red blood cells (sRBC) as targets, we demonstrate that phagocytosis is inhibited by HIV-1 infection in vitro. Inhibition is not due to downregulation of surface C′ receptors (R) or altered binding of C′-opsonized targets to HIV-1-infected MDM, suggesting a postreceptor-mediated mechanism of suppression. Having shown that increased levels of intracellular cAMP in uninfected MDM inhibit phagocytosis, we demonstrate that HIV-1 infection of MDM is associated with increased intracellular cAMP. Using the adenylate cyclase inhibitors 2′,5′-dideoxyadenosine and MDL-12,330A, we show that phagocytosis by HIV-1- infected MDM can be restored by inhibition of cAMP production. Defective p...