Host defense against Mycobacterium-avium complex.

Mycobacterium-avium complex (MAC) is an intracellular pathogen and the most common cause of widely disseminated bacterial infection in patients with the acquired immunodeficiency syndrome (AIDS). MAC is infrequently seen in other immunocompromised adults, suggesting that the host defense defect allowing for MAC infection is relatively unique for AIDS. A system was developed for studying the immune response to MAC infection, utilizing MAC isolated from patients with AIDS and monocytes from normal controls and patients with AIDS. Phagocytosis, superoxide anion (SOA) production, and killing were measured. Monocytes from normal controls and AIDS patients were identical with respect to phagocytosis of MAC. In contrast, baseline SOA production was elevated in monocytes from patients compared to normal monocytes and was minimally augmented in response to either phorbol myristate acetate or MAC. Fourteen-day kinetic studies revealed in patients and controls a biphasic pattern with 50-99% killing of AIDS-derived MAC initially, followed always by a rapid outgrowth of surviving bacilli. Despite a modest enhancement of MAC killing by normal but not patients' monocytes pretreated with either recombinant interferon-gamma or recombinant tumor necrosis factor-alpha, outgrowth of MAC was always observed in both, typically faster in patients than in controls. Even monocytes in the presence of lymphocytes stimulated with interleukin-2 did not demonstrate enhanced MAC killing. In contrast, high-titered anti-MAC immune serum derived from a patient with polymyositis and disseminated MAC significantly enhanced the killing of MAC by monocytes from both AIDS patients and healthy controls and prevented their outgrowth. These findings suggest that the host defense defect allowing for MAC infection appears not to reside in the monocyte and that the in vitro lymphocyte functions examined in this study do not appear to play a major role. What role specific antibody plays in vivo in preventing disseminated MAC is uncertain, but the lack of such antibody may help explain the propensity for AIDS patients to develop systemic infection.