T cells enhance production of IL-18 by monocytes in response to an intracellular pathogen.
We studied the effect of T cells on IL-18 production by human monocytes in response to Mycobacterium tuberculosis. Addition of activated T cells markedly enhanced IL-18 production by monocytes exposed to M. tuberculosis. This effect was mediated by a soluble factor and did not require cell-to-cell contact. The effect of activated T cells was mimicked by recombinant IFN-gamma and was abrogated by neutralizing Abs to IFN-gamma. IFN-gamma also enhanced the capacity of alveolar macrophages to produce IL-18 in response to M. tuberculosis, suggesting that this mechanism also operates in the lung during mycobacterial infection. IFN-gamma increased IL-18 production by increasing cleavage of pro-IL-18 to mature IL-18, as it enhanced caspase-1 activity but did not increase IL-18 mRNA expression. These findings suggest that activated T cells can contribute to the initial immune response by augmenting IL-18 production by monocytes in response to an intracellular pathogen.
Vankayalapati
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Center for Pulmonary and Infectious Disease Control, University of Texas Health Center, 11937 US Highway 271, Tyler, TX 75708, USA.
Wizel
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Lakey
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Zhang
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Coffee
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Griffith
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Barnes
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D020170:Caspase 1 / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology / Q000502:physiology; D020382:Interleukin-18 / Q000096:biosynthesis* / Q000235:genetics; D007424:Intracellular Fluid / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D008213:Lymphocyte Activation; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D012323:RNA Processing, Post-Transcriptional / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology*
D020382:Interleukin-18; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma; D020170:Caspase 1