Members of the Mycobacterium avium-intracellulare complex (MAC) can exist in a transparent or opaque colonial morphology when cultured on synthetic medium. An opaque variant was developed from a transparent strain of a clinical MAC isolate. Comparison of the two variants showed a greater ability of the transparent colonial variant to infect normal human monocytes as measured by growth in monocyte-bacteria cocultures. Further analyses indicated diminished ability of the transparent variant to induce extracellular secretion of interleukin (IL)-1 and IL-6, as well as membrane-associated IL-1 when compared with the opaque isotype. At the molecular level, induction of specific IL-1 alpha, IL-1 beta, and IL-6 mRNAs was consistent with the protein results. These results suggest that the virulent transparent MAC, as opposed to the avirulent opaque type, may escape host defenses by failing to induce IL-1 and IL-6, key factors in the initiation of a normal immune response.

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Using a rapid radiolabel assay, monocytes derived from the peripheral blood of normal donors were found to kill 40%-92% of inoculated Mycobacterium avium-intracellulare complex (MAC), an opportunistic pathogen commonly found in AIDS patients. However, bactericidal activity was significantly lower in 4-day culture-derived macrophages compared with matched monocyte cultures. The addition of interferon-gamma (IFN-gamma) to monocytes was found to inhibit the bactericidal activity of fresh monocytes. The number of bacteria recovered from fresh monocytes exposed to IFN-gamma was significantly higher than that in control cultures with MAC alone, suggesting that intracellular MAC growth could be stimulated by IFN-gamma. This enhancement of MAC survival and growth by IFN-gamma was not observed when culture-derived macrophages were used. Similar results were obtained with IFN-alpha/A2. These results indicate, therefore, that the innate efficiency of mycobacterial killing by monocytes can be down-regulated by IFN, but macrophages are not significantly affected.

In the present study, culture supernatants from larger granular lymphocytes (LGL) that were activated with Candida albicans antigens were shown to stimulate the ability of neutrophils to inhibit fungal growth. Identification of the activation factors showed that granulocyte-macrophage colony-stimulating factor (GM-CSF), a hematopoietic growth factor, was involved. Human peripheral blood mononuclear cells were fractionated by Percoll density centrifugation and each subpopulation of cells was stimulated with C albicans yeast cells. GM-CSF was produced in those fractions enriched for LGL, but not T lymphocytes or adherent monocytes. Additionally, the phenotype of the GM-CSF-producing cell was found to be CD2+, CD16+, HLA-DR+, and negative for CD4, CD8, and CD15. Kinetic studies demonstrated that GM- CSF appeared in the supernatants within 2 days of culture and continued to be produced up to 7 days. Optimal stimulation of LGL was seen at a ratio of 3 heat-killed C albicans yeast cells per LGL. Thus, LGL play an important role in host defense against this opportunistic pathogen by producing cytokines, including GM-CSF, which in turn activates the fungicidal activity of neutrophils.