HIV Infection Impairs Macrophage Interaction with Histoplasma capsulatum

We have demonstrated that monocyte-derived macrophages (M f ) from HIV 1 individuals are deficient in their capacity to phagocytose Histoplasma capsulatum (Hc) yeasts, and are more permissive for the intracellular growth of Hc. To determine whether these defects in M f function were caused by HIV infection of the M f and/or by pathological events associated with HIV infection, cultured normal human M f were infected with the HIV-1 BaL strain. Virus production, quantified by reverse transcriptase activity and p24 antigen, was evident on day 8 after infection and peaked on day 16. On days 12, 16, and 20 after infection, HIV-1–infected M f were deficient in their capacity to recognize and bind Hc yeasts compared with control M f , and also were more permissive for the intracellular growth of Hc. Culture of normal M f with the envelope glycoprotein gp120 inhibited phagocytosis of Hc yeasts by M f in a concentration-dependent manner, but did not cause more rapid intracellular growth of Hc. Normal M f cultured in the serum of HIV 1 individuals with impaired M f function subsequently were deficient in their capacity to phagocytose Hc yeasts, and were more permissive for the intracellular growth of yeasts compared with M f cultured in normal serum. Conversely, culture of normal M f in the serum of HIV 1 patients with normal M f function did not affect the interaction of Hc yeasts with M f . Moreover, when M f from HIV 1 individuals that were initially defective in host defense against Hc were cultured in normal HIV 2 serum, normal M f function was demonstrated. Adsorption of gp120 from the serum of two HIV 1 patients removed the capacity of the serum to cause a M f defect in phagocytosis of Hc, but had no effect on the capacity of the serum to cause accelerated intracellular growth. These data demonstrate that observed defects in M f interaction with Hc yeasts may be caused by gp120 and other, as yet unknown serum component(s) probably released into serum by HIV-infected cells. ( J. Clin. Invest. 1997. 100:1465– 1474.)