IL-10 converts human dendritic cells into macrophage-like cells with increased antibacterial activity against virulent Mycobacterium tuberculosis.
Dendritic cells (DC) are unique in their ability to initiate a primary immune response by the presentation of soluble Ags to T cells. Recent studies have shown that DC also phagocytose particulate Ags including the intracellular pathogen Mycobacterium tuberculosis. However, it is not known whether DC contain the growth of intracellular organisms or allow unlimited replication. To address this question, we infected human DC with a virulent strain of M. tuberculosis and monitored the intracellular growth. The bacteria grew two orders of magnitude within 7 days of culture. Among cytokines known to modulate mycobacterial growth particularly in murine macrophages (TNF-alpha, IFN-gamma, TGF-beta, IL-4), only IL-10 modulated the growth in human DC. This effect was specific for immature dendritic cells, as IL-10 did not induce growth inhibition in human macrophages. In searching for the mechanism of growth inhibition, we found that IL-10 induces the down-regulation of the DC marker CD1, while the macrophage marker CD14 was up-regulated. Functionally, IL-10-treated cells had a reduced capacity to induce an alloresponse, but phagocytic uptake of M. tuberculosis was more efficient. We also show that DC are inferior to macrophages in containing mycobacterial growth. These findings show that IL-10 converts DC into macrophage-like cells, thereby inducing the growth inhibition of an intracellular pathogen. At the site of a local immune response, such as a tuberculous granuloma, IL-10 might therefore participate in the composition of the cellular microenvironment by affecting the maturity and function of DC.
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Institut für Klinische Mikrobiologie, Immunologie und Hygiene der Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
Röllinghoff
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Stenger
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D000900:Anti-Bacterial Agents / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D006131:Growth Inhibitors / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000502:physiology; D016753:Interleukin-10 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000254:growth & development* / Q000276:immunology* / Q000472:pathogenicity; D010587:Phagocytosis / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014774:Virulence
D000900:Anti-Bacterial Agents; D006131:Growth Inhibitors; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma