Cytokine and contact-dependent activation of natural killer cells by influenza A or Sendai virus-infected macrophages.
NK cells participate in innate immune responses by secreting gamma interferon (IFN-gamma) and by destroying virus-infected cells. Here the interaction between influenza A or Sendai virus-infected macrophages and NK cells has been studied. A rapid, cell-cell contact-dependent production of IFN-gamma from NK cells cultured with virus-infected macrophages was observed. Expression of the MHC class I-related chain B (MICB) gene, a ligand for NK cell-activating receptor NKG2D, was upregulated in virus-infected macrophages suggesting a role for MICB in the activation of the IFN-gamma gene in NK cells. IL12Rbeta2, IL18R and T-bet mRNA synthesis was enhanced in NK cells cultured with virus-infected macrophages. Upregulation of these genes was dependent on macrophage-derived IFN-alpha. In contrast to IL12Rbeta2, expression of WSX-1/TCCR, a receptor for IL27, was reduced in NK cells in response to virus-induced IFN-alpha. In conclusion, these results show that virus-infected macrophages activate NK cells via cytokines and direct cellular interactions and further emphasize the role of IFN-alpha in the activation of innate immunity.
Sirén
Jukka
J
Department of Microbiology, National Public Health Institute, Helsinki, Finland.
Sareneva
Timo
T
Department of Microbiology, National Public Health Institute, Helsinki, Finland.
Pirhonen
Jaana
J
Department of Microbiology, National Public Health Institute, Helsinki, Finland.
Strengell
Mari
M
Department of Microbiology, National Public Health Institute, Helsinki, Finland.
Veckman
Ville
V
Department of Microbiology, National Public Health Institute, Helsinki, Finland.
Julkunen
Ilkka
I
Department of Microbiology, National Public Health Institute, Helsinki, Finland.
Matikainen
Sampsa
S
Department of Microbiology, National Public Health Institute, Helsinki, Finland.
D002450:Cell Communication; D018920:Coculture Techniques; D016207:Cytokines / Q000502:physiology*; D005786:Gene Expression Regulation; D015395:Histocompatibility Antigens Class I; D006801:Humans; D009980:Influenza A virus / Q000502:physiology*; D016898:Interferon-alpha / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000502:physiology* / Q000821:virology; D011506:Proteins / Q000235:genetics; D029082:Sendai virus / Q000502:physiology*
D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D016898:Interferon-alpha; C098080:MICB antigen; D011506:Proteins; D007371:Interferon-gamma