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I E Flesch

Publications and source records attributed to I E Flesch.

28 records · Page 2Linked to original sources
PubMed1990

Stimulation of antibacterial macrophage activities by B-cell stimulatory factor 2 (interleukin-6).

Mononuclear phagocytes provide the major habitat of intracellular bacteria, including Mycobacterium tuberculosis and Mycobacterium bovis. The capacity of B-cell stimulatory factor 2 (interleukin-6 [IL-6]) to activate tuberculostatic functions was investigated by using murine bone marrow-derived macrophages (BMM phi). BMM phi stimulated with recombinant IL-6 and subsequently infected with M. bovis organisms failed to inhibit mycobacterial growth. In contrast, marked tuberculostasis was induced by IL-6 in BMM phi that were already infected with M. bovis, indicating that IL-6 has a macrophage-activating function.

Animals↗
PubMed1990

Activation of tuberculostatic macrophage functions by gamma interferon, interleukin-4, and tumor necrosis factor.

The capacity of the cytokines gamma interferon (IFN-gamma), interleukin-4 (IL-4), and tumor necrosis factor (TNF) to activate tuberculostatic functions in murine bone marrow-derived macrophages (BMM phi) was investigated. In confirmation of earlier findings, IFN-gamma rendered BMM phi capable of inhibiting subsequent infection with Mycobacterium bovis. In contrast, IL-4 and TNF failed to inhibit mycobacterial growth. However, in already infected BMM phi, tuberculostasis was induced by subsequent stimulation with IL-4. Although TNF alone was ineffective, it showed synergy with IFN-gamma in the stimulation of tuberculostasis. Our data suggest that not only IFN-gamma but also IL-4 and TNF participate in the control of mycobacterial growth.

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PubMed1989

Fungicidal activity of IFN-gamma-activated macrophages. Extracellular killing of Cryptococcus neoformans.

Cryptococcus neoformans is an encapsulated yeast-form fungus which causes pulmonary and meningeal infections preferentially in the immunocompromised host. It is thought that cell-mediated immunity is important for acquired resistance against cryptococcosis with activated macrophages as the final effector cells. However, specific polysaccharides in the capsule of C. neoformans protect the fungus from adherence to phagocytes and from subsequent phagocytosis. We have studied extracellular killing of C. neoformans by IFN-gamma-activated macrophages and their products. Murine bone marrow-derived macrophages stimulated with rIFN-gamma for 24 h were able to effectively suppress the growth of C. neoformans and the effect of IFN-gamma was augmented by LPS. Killing of C. neoformans was also achieved by cell-free supernatants from bone marrow-derived macrophages stimulated with IFN-gamma plus LPS. Our results indicate that killing of C. neoformans by activated macrophages is independent from toxic oxygen radicals and mediated by secreted protein(s) of apparent molecular mass of 15 and 30 kDa. These findings indicate that activated macrophages play a major role in host defense, although the fungus resists phagocytosis and remains in the extracellular milieu.

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PubMed1989

Cell-mediated immunity to mycobacteria: a double-sided sword?

Mycobacteria are intracellular pathogens capable of replicating in resting macrophages. Specific helper T lymphocytes which activate antimycobacterial capacities in infected macrophages represent an important constituent of acquired resistance. In addition, cytolytic T lymphocytes may contribute to resistance. On the other hand, lysis of infected host cells may also comprise autoaggressive consequences. Recent evidence suggest that T cells with specificity for mycobacterial heat shock proteins are involved in the antimycobacterial immune response. Heat shock proteins are evolutionarily highly conserved and cross-reactivity between microbial and mammalian molecules may occur on the B-cell and T-cell level. Thus, T cells directed against shared epitopes of mycobacterial and autologous origin could initiate autoimmune reactions.

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PubMed1988

The role of T cell--macrophage interactions in tuberculosis.

Acquired resistance against tuberculosis paradigmatically depends on specific T lymphocytes and mononuclear phagocytes. The etiological agent, Mycobacterium tuberculosis is capable of replicating in mononuclear phagocytes which act both as habitat and as effectors of protection. Upon interaction with antigen-specific T lymphocytes infected mononuclear phagocytes acquire tuberculostatic activities. Here, data from experimental tuberculosis studies in mice are summarized which show that: interleukins produced by cloned T cells and recombinant interferon-gamma are capable of activating tuberculostatic capacities in macrophages; both CD4 and CD8 T cells, after adequate stimulation, produce interferon-gamma; CD8 T cells lyse macrophages in an antigen-specific way; not only CD8 but also CD4 T cells possess an antigen-specific cytolytic potential; lysis of infected macrophages results in mycobacterial growth inhibition. Evidence is also presented that tuberculostatic activities of activated macrophages depend on phagosome-lysosome fusion and are independent of reactive oxygen metabolites and that some strains of M. tuberculosis are resistant against interferon-gamma activities macrophages. These findings suggest that both helper and cytolytic T cells participate in the immune response to tuberculosis and that similar T cell mechanisms contribute to resistance as well as pathogenesis. Protection against tuberculosis, therefore, depends on subtle coordination of the immune response.

Animals↗
PubMed1988

Attempts to characterize the mechanisms involved in mycobacterial growth inhibition by gamma-interferon-activated bone marrow macrophages.

Bone marrow-derived murine macrophages are able to inhibit the growth of Mycobacterium bovis and of some strains of M. tuberculosis after stimulation with either recombinant gamma interferon (rIFN-gamma) or lymphokines from antigen-specific T-cell clones. To elucidate the mechanism(s) involved in antimycobacterial activity, macrophages were infected with M. bovis in the presence of agents thought to influence the antimicrobial effects of phagocytes. Scavengers of toxic oxygen metabolites failed to influence the capacity of IFN-gamma-activated bone marrow macrophages to inhibit the growth of M. bovis. Suramin slightly affected mycobacterial growth in IFN-gamma-activated macrophages, and chloroquine markedly induced growth inhibition of M. bovis in unstimulated macrophages. We conclude that growth inhibition of M. bovis by IFN-gamma-activated macrophages is an oxygen-independent process.

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