Coordinated and distinct roles for IFN-alpha beta, IL-12, and IL-15 regulation of NK cell responses to viral infection.
NK cell cytotoxicity, IFN-gamma expression, proliferation, and accumulation are rapidly induced after murine CMV infections. Under these conditions, the responses were shown to be elicited in overlapping populations. Nevertheless, there were distinct signaling molecule requirements for induction of functions within the subsets. IL-12/STAT4 was critical for NK cell IFN-gamma expression, whereas IFN-alphabeta/STAT1 were required for induction of cytotoxicity. The accumulation/survival of proliferating NK cells was STAT4-independent but required IFN-alphabeta/STAT1 induction of IL-15. Taken together, the results define the coordinated interactions between the cytokines IFN-alphabeta, IL-12, and IL-15 for activation of protective NK cell responses during viral infections, and emphasize these factors' nonredundant functions under in vivo physiological conditions.
Nguyen
Khuong B
KB
Deparment of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA.
Salazar-Mather
Thais P
TP
Dalod
Marc Y
MY
Van Deusen
Jeffrey B
JB
Wei
Xiao-qing
XQ
Liew
Foo Y
FY
Caligiuri
Michael A
MA
Durbin
Joan E
JE
Biron
Christine A
CA
D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology; D007274:Injections, Intraperitoneal; D016898:Interferon-alpha / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016899:Interferon-beta / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019409:Interleukin-15 / Q000096:biosynthesis / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000276:immunology; D050794:STAT1 Transcription Factor; D050797:STAT4 Transcription Factor; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology
D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D019409:Interleukin-15; D050794:STAT1 Transcription Factor; D050797:STAT4 Transcription Factor; C494080:Stat1 protein, mouse; C494091:Stat4 protein, mouse; D015534:Trans-Activators; D018664:Interleukin-12; D016899:Interferon-beta; D007371:Interferon-gamma