HIV-1 INFECTION OF HUMAN MACROPHAGES IMPAIRS PHAGOCYTOSIS AND KILLINGOF TOXOPLASMA-GONDII

The susceptibility of patients with AIDS to certain opportunistic infe ctions is due to defective cell-mediated immunity. The contribution of direct infection of macrophages with HIV-1 to this defect is unknown. To address this issue, we infected normal human monocyte-derived macr ophages with a monocytotropic strain of HIV-1 and examined their abili ty to phagocytose and kill the opportunistic pathogen, Toxoplasma gond ii. Phagocytosis of heat-killed T. gondii was reduced in HIV-infected macrophages compared with mock-infected controls, Opsonization of heal -killed T. gondii increased phagocytosis by both mock- and HIV-infecte d macrophages, but phagocytosis in HIV-infected cultures remained lowe r than in controls. Internalization of live T. gondii by macrophages w as unaffected by HIV infection. Intracellular replication of live T. g ondii was enhanced by HIV infection, as shown in four experiments, eac h using monocyte-derived macrophages from a different donor. Treatment of HIV-infected macrophages with IFN-gamma decreased parasite replica tion but not to control levels. These findings suggest that infection of macrophages by HIV may be a contributing factor to the reactivation of T.gondii infection in patients with AIDS.