| Literature DB >> 8805654 |
Abstract
Legionella pneumophila is a facultative intracellular pathogen that parasitizes human alveolar macrophages and blood monocytes recruited to the lungs. The inhibitory cytokines IL-10, TGF-beta, and IL-4 generally deactivate macrophages and permit enhanced microbial growth in some models of intracellular infection, but their effects on human alveolar macrophages are unknown. We hypothesized that inhibitory cytokines could facilitate the infection of human alveolar macrophages and monocytes by virulent intracellular lung pathogens. Therefore, we tested the effects of IL-10, TGF-beta, and IL-4 in an in vitro model of human alveolar macrophage and monocyte infection with L. pneumophila. We found that unstimulated alveolar macrophages supported over 100-fold greater L. pneumophila growth than did unstimulated monocytes. IL-10 treatment significantly enhanced L. pneumophila growth in monocytes, and completely reversed the protective effect of IFN-gamma against intracellular L. pneumophila replication. IL-10 had similar but less potent effects on alveolar macrophages. In contrast, TGF-beta and IL-4 had no significant effects on L. pneumophila growth in resting or IFN-gamma-activated monocytes or alveolar macrophages. IL-10 blocked TNF-alpha production by infected cells, but exogenous TNF-alpha did not reverse the activating defect in cells cocultured with IFN-gamma and IL-10. Finally, L. pneumophila-infected monocytes produced substantially more IL-10 than did infected alveolar macrophages. In summary, IL-10 significantly enhances the growth of L. pneumophila in human monocytes, reverses the protective effect of IFN-gamma, blocks TNF-alpha secretion, and is secreted by infected monocytes and alveolar macrophages. Induction of IL-10 may be a virulence mechanism that promotes intracellular bacterial replication in human legionellosis.Entities:
Mesh：
Substances：
Year: 1996 PMID： 8805654
Source DB: PubMed Journal: J Immunol ISSN： 0022-1767 Impact factor: 5.422