Abstract
We determined whether human NK cells could contribute to immune defenses against Mycobacterium tuberculosis through production of IL-22. CD3(-)CD56(+) NK cells produced IL-22 when exposed to autologous monocytes and gamma-irradiated M. tuberculosis, and this depended on the presence of IL-15 and IL-23, but not IL-12 or IL-18. IL-15-stimulated NK cells expressed 10.6 times more DAP10 mRNA compared with control NK cells, and DAP10 siRNA inhibited IL-15-mediated IL-22 production by NK cells. Soluble factors produced by IL-15-activated NK cells inhibited growth of M. tuberculosis in macrophages, and this effect was reversed by anti-IL-22. Addition of rIL-22 to infected macrophages enhanced phagolysosomal fusion and reduced growth of M. tuberculosis. We conclude that NK cells can contribute to immune defenses against M. tuberculosis through production of IL-22, which inhibits intracellular mycobacterial growth by enhancing phagolysosomal fusion. IL-15 and DAP-10 elicit IL-22 production by NK cells in response to M. tuberculosis.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Humans
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Interleukin-12 / pharmacology
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Interleukin-15 / pharmacology
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Interleukin-18 / pharmacology
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Interleukin-22
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Interleukin-23 / pharmacology
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Interleukins / immunology*
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Interleukins / metabolism
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Interleukins / pharmacology
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Killer Cells, Natural / drug effects
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism
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Killer Cells, Natural / microbiology
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Macrophages / drug effects
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Macrophages / immunology*
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Macrophages / metabolism
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Macrophages / microbiology
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Mycobacterium tuberculosis / drug effects
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Mycobacterium tuberculosis / growth & development
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Mycobacterium tuberculosis / immunology*
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Phagosomes / drug effects
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Phagosomes / immunology*
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Phagosomes / metabolism
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Phagosomes / microbiology
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RNA, Messenger / agonists
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RNA, Messenger / immunology
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RNA, Messenger / metabolism
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RNA, Small Interfering / immunology
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RNA, Small Interfering / metabolism
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Receptors, Immunologic / agonists
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Receptors, Immunologic / genetics
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Receptors, Immunologic / immunology
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Receptors, Immunologic / metabolism
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Recombinant Proteins / pharmacology
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Tuberculosis / immunology*
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Tuberculosis / microbiology
Substances
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HCST protein, human
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Interleukin-15
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Interleukin-18
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Interleukin-23
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Interleukins
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RNA, Messenger
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RNA, Small Interfering
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Receptors, Immunologic
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Recombinant Proteins
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Interleukin-12