Mycobacteria are major causes of opportunistic infection in the acquired immunodeficiency syndrome (AIDS). By 1991, approximately 146,000 AIDS patients in the United States will have developed infections with Mycobacterium avium or Mycobacterium tuberculosis. More completer understanding of the pathogenesis and pathophysiology of mycobacterial infection is essential to devise new strategies for prevention and treatment since existing modalities often are inadequate. The proposal tests two interconnected hypotheses: a) the systemic effects of intracellular parasitism by M. avium are mitigated by blockade in IL-1/TNF production; but there is concurrent compromise of effector and accessory function of mononuclear phagocytes; and b) infection with human immunodeficiency virus (HIV) is associated with a primary defect in killing of M. tuberculosis and M. avium by mononuclear phagocytes, possibly compounded by suboptimal responses to macrophage activating factors.
Specific aims to test these hypotheses are: 1) To identify activating factors which promote growth inhibition or killing of M. avium, M. tuberculosis, Toxoplasma gondii and tumors by mononuclear phagocytes from healthy donors and to examine the association of intracellular growth with serovar, plasmid content, mouse virulence, and source of M. avium isolates; 2) To determine whether M. avium and M. tuberculosis infection of mononuclear phagocytes from healthy subjects interferes with cellular secretory, immunoregulatory and effector functions; and 3) To examine mycobacterial phagocytosis and growth inhibition by mononuclear phagocytes and augmentation of effector functions by macrophage activating factors (MAF) subjects with HIV infection. This research is health-related.
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