ABSTRACT
Interleukin-12 (IL-12) is a key cytokine in the immune response to infection with Mycobacterium avium complex (MAC). Human immunodeficiency virus infection, a predisposing factor for disseminated MAC infection, causes a drop of bioactive IL-12(p70), mainly by decreasing the constitutive production of p35. IL-12(p40) and tumor necrosis factor-alpha (TNF-alpha) levels in supernatants of MAC-infected human monocyte-derived macrophages with intracellular growth rates were compared. Isolates from AIDS patients showed high growth rates and induced low TNF-alpha but high IL-12(p40) levels. In contrast, environmental isolates with fast growth rates induced only low levels of IL-12(p40) secretion. The increased IL-12(p40) stimulus seen with the clinical isolates could lead to a p40 surplus, which, alone or as the (p40)2 homodimer, has immunosuppressive properties. An immunosuppressive effect of MAC isolates may be an important advantage for their survival in vivo and may explain the contribution of MAC infection to the progression of AIDS.
Subject(s)
Acquired Immunodeficiency Syndrome/microbiology , Interleukin-12/metabolism , Macrophages/immunology , Monocytes/immunology , Mycobacterium avium Complex/immunology , Enzyme-Linked Immunosorbent Assay , Humans , Immune Tolerance , Macrophages/cytology , Macrophages/microbiology , Monocytes/cytology , Monocytes/microbiology , Phenotype , Tumor Necrosis Factor-alpha/metabolismABSTRACT
The capacity of 20 Mycobacterium avium complex isolates to multiply intracellularly in human monocyte-derived macrophages was assessed and correlated to the clinical relevance of each isolate and its reactivity with several candidate genetic virulence markers. The strongest correlation with a virulence phenotype was found for a conserved coding sequence of the macrophage-induced gene mig identified by a specific mig restriction fragment length polymorphism type.
