MODULATION OF THE EFFECTOR FUNCTION OF HUMAN MACROPHAGES FOR HISTOPLASMA-CAPSULATUM BY HIV-1 - ROLE OF THE ENVELOPE GLYCOPROTEIN GP120

We have demonstrated that monocyte-derived macrophages (M phi) from HI V+ individuals are deficient in their capacity to phagocytose Histopla sma capsulatum (He) yeasts, and are more permissive for the intracellu lar growth of He. To determine whether these defects in M phi function were caused by HIV infection of the M phi and/or by pathological even ts associated with HIV infection, cultured normal human M phi were inf ected with the HIV-1(BaL) strain. Virus production, quantified by reve rse transcriptase activity and p24 antigen, was evident on day 8 after infection and peaked on day 16. On days 12, 16, and 20 after infectio n, HIV-1-infected M phi were deficient in their capacity to recognize and bind He yeasts compared with control M phi, and also were more per missive for the intracellular growth of He. Culture of normal M phi wi th the envelope glycoprotein gp120 inhibited phagocytosis of Hc yeasts by M phi in a concentration-dependent manner, but did not cause more rapid intracellular growth of He. Normal M phi cultured in the serum o f HIV+ individuals with impaired M phi function subsequently were defi cient in their capacity to phagocytose He yeasts, and were more permis sive for the intracellular growth of yeasts compared with M phi cultur ed in normal serum. Conversely, culture of normal M phi in the serum o f HIV+ patients with normal M phi function did not affect the interact ion of He yeasts with M phi. Moreover, when M phi from HIVS individual s that were initially defective in host defense against He were cultur ed in normal HIV-serum, normal M phi function was demonstrated. Adsorp tion of gp120 from the serum of two HIV+ patients removed the capacity of the serum to cause a M phi defect in phagocytosis of He, but had n o effect on the capacity of the serum to cause accelerated intracellul ar growth. These data demonstrate that observed defects in M phi inter action with He yeasts may be caused by gp120 and other, as yet unknown serum component(s) probably released into serum by HIV-infected cells .