title: The natural killer cell response to West Nile virus in young and old individuals with or without a prior history of infection.
abstract: West Nile virus (WNV) typically leads to asymptomatic infection but can cause severe neuroinvasive disease or death, particularly in the elderly. Innate NK cells play a critical role in antiviral defenses, yet their role in human WNV infection is poorly defined. Here we demonstrate that NK cells mount a robust, polyfunctional response to WNV characterized by cytolytic activity, cytokine and chemokine secretion. This is associated with downregulation of activating NK cell receptors and upregulation of NK cell activating ligands for NKG2D. The NK cell response did not differ between young and old WNV-naïve subjects, but a history of symptomatic infection is associated with more IFN-γ producing NK cell subsets and a significant decline in a specific NK cell subset. This NK repertoire skewing could either contribute to or follow heightened immune pathogenesis from WNV infection, and suggests that NK cells could play an important role in WNV infection in humans.
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Stanford Immunology, Stanford University School of Medicine, Stanford, California, United States of America.|Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Dara M
authors.initials: DM
authors.lastname: Strauss-Albee
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Julian Q
authors.initials: JQ
authors.lastname: Zhou
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Anna
authors.initials: A
authors.lastname: Malawista
authors.affiliation: Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, United States of America.
authors.forename: Melissa N
authors.initials: MN
authors.lastname: Garcia
authors.affiliation: Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, United States of America.
authors.forename: Kristy O
authors.initials: KO
authors.lastname: Murray
authors.affiliation: Stanford Immunology, Stanford University School of Medicine, Stanford, California, United States of America.|Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Blish
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, United States of America.|Program on Human Translational Immunology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Ruth R
authors.identifier: http://orcid.org/0000-0002-8661-4454
authors.initials: RR
authors.lastname: Montgomery
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D058070:Asymptomatic Diseases; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008875:Middle Aged; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000235:genetics / Q000276:immunology; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000276:immunology*; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000235:genetics / Q000276:immunology; D055629:Natural Cytotoxicity Triggering Receptor 2 / Q000235:genetics / Q000276:immunology; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000235:genetics / Q000276:immunology; D061251:Primary Cell Culture; D012720:Severity of Illness Index; D014901:West Nile Fever / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000821:virology; D014902:West Nile virus / Q000254:growth & development / Q000276:immunology*
chemical_list: D015703:Antigens, CD; C527085:KLRK1 protein, human; C112260:NCR1 protein, human; C112837:NCR2 protein, human; C431710:NCR3 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D055655:NK Cell Lectin-Like Receptor Subfamily K; D055627:Natural Cytotoxicity Triggering Receptor 1; D055629:Natural Cytotoxicity Triggering Receptor 2; D055628:Natural Cytotoxicity Triggering Receptor 3; D007371:Interferon-gamma