Abstract
We studied the role of NK cell-activating receptors and their ligands in the lysis of mononuclear phagocytes infected with the intracellular pathogen Mycobacterium tuberculosis. Expression of the activating receptors NKp30, NKp46, and NKG2D were enhanced on NK cells by exposure to M. tuberculosis-infected monocytes, whereas expression of DNAX accessory molecule-1 and 2B4 was not. Anti-NKG2D and anti-NKp46 inhibited NK cell lysis of M. tuberculosis-infected monocytes, but Abs to NKp30, DNAX accessory molecule-1, and 2B4 had no effect. Infection of monocytes up-regulated expression of the NKG2D ligand, UL-16 binding protein (ULBP)1, but not expression of ULBP2, ULBP3, or MHC class I-related chain A or chain B. Up-regulation of ULBP1 on infected monocytes was dependent on TLR2, and anti-ULBP1 abrogated NK cell lysis of infected monocytes. The dominant roles of NKp46, NKG2D, and ULBP1 were confirmed for NK cell lysis of M. tuberculosis-infected alveolar macrophages. We conclude that NKp46 and NKG2D are the principal receptors involved in lysis of M. tuberculosis-infected mononuclear phagocytes, and that ULBP1 on infected cells is the major ligand for NKG2D. Furthermore, TLR2 contributes to up-regulation of ULBP1 expression.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Carrier Proteins / biosynthesis
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Carrier Proteins / genetics
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Carrier Proteins / immunology
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Carrier Proteins / metabolism
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Cells, Cultured
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GPI-Linked Proteins
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Histocompatibility Antigens Class I / biosynthesis
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Histocompatibility Antigens Class I / genetics
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Histocompatibility Antigens Class I / immunology
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Histocompatibility Antigens Class I / metabolism
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Humans
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Intracellular Fluid / immunology
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Intracellular Fluid / microbiology*
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Intracellular Signaling Peptides and Proteins
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism
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Ligands
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Macrophages, Alveolar / immunology*
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Macrophages, Alveolar / microbiology*
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Membrane Glycoproteins / physiology*
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Membrane Proteins
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Monocytes / immunology*
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Monocytes / metabolism
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Monocytes / microbiology*
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Mycobacterium tuberculosis / immunology
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NK Cell Lectin-Like Receptor Subfamily K
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Natural Cytotoxicity Triggering Receptor 1
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Receptors, Immunologic / metabolism
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Receptors, Immunologic / physiology*
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Receptors, Natural Killer Cell
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Up-Regulation / immunology
Substances
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Carrier Proteins
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GPI-Linked Proteins
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Histocompatibility Antigens Class I
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Intracellular Signaling Peptides and Proteins
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KLRK1 protein, human
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Ligands
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Membrane Glycoproteins
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Membrane Proteins
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NCR1 protein, human
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NK Cell Lectin-Like Receptor Subfamily K
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Natural Cytotoxicity Triggering Receptor 1
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Receptors, Immunologic
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Receptors, Natural Killer Cell
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ULBP1 protein, human