The NKp46 receptor contributes to NK cell lysis of mononuclear phagocytes infected with an intracellular bacterium.
We used human tuberculosis as a model to investigate the role of NK cytotoxic mechanisms in the immune response to intracellular infection. Freshly isolated NK cells and NK cell lines from healthy donors lysed Mycobacterium tuberculosis-infected monocytes to a greater extent than uninfected monocytes. Lysis of infected monocytes was associated with increased expression of mRNA for the NKp46 receptor, but not the NKp44 receptor. Antisera to NKp46 markedly inhibited lysis of infected monocytes. NK cell-mediated lysis was not due to reduced expression of MHC class I molecules on the surface of infected monocytes or to enhanced production of IL-18 or IFN-gamma. NK cell lytic activity against M. tuberculosis-infected monocytes and NKp46 mRNA expression were reduced in tuberculosis patients with ineffective immunity to M. tuberculosis compared with findings in healthy donors. These observations suggest that 1) the NKp46 receptor participates in NK cell-mediated lysis of cells infected with an intracellular pathogen, and 2) the reduced functional capacity of NK cells is associated with severe manifestations of infectious disease.
Vankayalapati
Ramakrishna
R
Center for Pulmonary and Infectious Disease Control, University of Texas Health Center, Tyler, TX 75708, USA.
Wizel
Benjamin
B
Weis
Stephen E
SE
Safi
Hassan
H
Lakey
David L
DL
Mandelboim
Ofer
O
Samten
Buka
B
Porgador
Angel
A
Barnes
Peter F
PF
D002460:Cell Line; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007424:Intracellular Fluid / Q000276:immunology* / Q000382:microbiology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000382:microbiology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D055627:Natural Cytotoxicity Triggering Receptor 1; D055629:Natural Cytotoxicity Triggering Receptor 2; D010586:Phagocytes / Q000276:immunology* / Q000382:microbiology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D014376:Tuberculosis / Q000276:immunology
D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D007106:Immune Sera; C112260:NCR1 protein, human; C112837:NCR2 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; D055629:Natural Cytotoxicity Triggering Receptor 2; D012333:RNA, Messenger; D011971:Receptors, Immunologic