title: Both NK cell-intrinsic and -extrinsic STAT1 signaling are required for NK cell response against vaccinia virus.
abstract: NK cells play an important role in innate immune control of the infection with vaccinia virus (VV). However, it remains incompletely defined how the activation of NK cells in response to VV is regulated. In this study, we showed that STAT1 was critical for NK cell activation upon VV infection and the subsequent clearance of VV infection in vivo. We further demonstrated that STAT1 signaling in both NK and accessory cells such as dendritic cells was required for efficient NK cell activation upon VV infection. Mechanistically, STAT1 signaling in dendritic cells promoted the expression of NKG2D ligands, which is required for NK cell activation via the NKG2D pathway. Taken together, our data suggest that STAT1 mediates anti-VV effect by promoting NK cell activation through both NK-intrinsic and extrinsic mechanisms and may provide insights into the design of effective NK cell-based therapies for viral infections.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Carl
authors.initials: C
authors.lastname: Fortin
authors.forename: Xiaopei
authors.initials: X
authors.lastname: Huang
authors.forename: Yiping
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000818:Animals; D002460:Cell Line; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology / Q000821:virology; D005260:Female; D007113:Immunity, Innate / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D050794:STAT1 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D014615:Vaccinia / Q000235:genetics / Q000276:immunology / Q000473:pathology; D014616:Vaccinia virus / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse