Differential Release of Interleukin (IL)-1 , IL-1 , and IL-6 from Normal Human Monocytes Stimulated with a Virulent and an Avirulent Isogenic Variant of Mycobacterium avium-intracellulare Complex

Abstract

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.

Differential Expression of Gamma Interferon mRNA Induced by Attenuated and VirulentMycobacterium tuberculosisin Guinea Pig Cells afterMycobacterium bovisBCG Vaccination

“…In both control and AIDS patients, more IL-1␤ was released after the infection of monocytes with the less virulent M. avium (16). Similarly, infection of human monocytes or macrophages with virulent M. avium downregulated the production of proinflammatory cytokines (IL-1␤, TNF-␣, IL-6, and granulocyte-macrophage colony-stimulating factor) compared to that by cells infected with the less virulent strain (32). Studies with mice revealed that lipoarabinomannan derived from an attenuated strain of M. tuberculosis induced macrophage activation and TNF-␣ production, whereas lipoarabinomannan from the virulent Erdman strain was less stimulatory (2).…”

“…It has been demonstrated that TNF-␣ plays an important role in the formation and maintenance of the granuloma and, along with IFN-␥, activates macrophages to produce effector molecules such as toxic oxygen and nitrogen intermediates (21). Interference with the production of appropriate mediators by lymphocytes and macrophages might be one of the pathogenic mechanisms employed by some mycobacteria (32).…”

Pulmonary Infection of Mycobacterium aviumintracellulare Complex with Simultaneous Organizing Pneumonia

“…MAC has been reported to induce the production of certain cytokines, including interleukin-1, interleukin-6, tumor necrosis factor-alpha , granulocyte-monocyte colonystimulating factor, and granulocyte colony-stimulating factor (10)(11)(12)(13) (15). In the present case, the ratio was higher than 1 ( Table 1).…”

Induction of IL-1 , IL-6, TNF- , GM-CSF and G-CSF in human macrophages by smooth transparent and smooth opaque colonial variants of Mycobacterium avium

“…18 reported that SmT and SmD variants induced a differential release of IL-1 a, IL-lp and IL-6 from nornial human monocytes and suggested that disturbances of cytokine production could contribute to MAC survival within cells, and then establish the infection. The aim of this study was to examine the production of cytokines from SmD-or SmT-infected monocytederived human macrophages, for a more complete evaluation of the release of these immunoregulatory proteins following MAC stimulation.…”