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.
MeSH terms
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Adult
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Age Factors
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Aged
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Aged, 80 and over
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Antigens, CD / genetics
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Antigens, CD / immunology
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Asymptomatic Diseases
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Female
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Gene Expression Regulation
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Humans
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Immunity, Innate*
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Immunophenotyping
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Interferon-gamma / genetics
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Interferon-gamma / immunology
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / virology
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Lymphocyte Activation
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Lymphocyte Count
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Middle Aged
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NK Cell Lectin-Like Receptor Subfamily C / genetics
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NK Cell Lectin-Like Receptor Subfamily C / immunology
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NK Cell Lectin-Like Receptor Subfamily K / genetics
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NK Cell Lectin-Like Receptor Subfamily K / immunology*
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Natural Cytotoxicity Triggering Receptor 1 / genetics
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Natural Cytotoxicity Triggering Receptor 1 / immunology
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Natural Cytotoxicity Triggering Receptor 2 / genetics
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Natural Cytotoxicity Triggering Receptor 2 / immunology
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Natural Cytotoxicity Triggering Receptor 3 / genetics
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Natural Cytotoxicity Triggering Receptor 3 / immunology
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Primary Cell Culture
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Severity of Illness Index
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West Nile Fever / diagnosis
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West Nile Fever / genetics
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West Nile Fever / immunology*
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West Nile Fever / virology
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West Nile virus / growth & development
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West Nile virus / immunology*
Substances
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Antigens, CD
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KLRK1 protein, human
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NCR1 protein, human
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NCR2 protein, human
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NCR3 protein, human
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NK Cell Lectin-Like Receptor Subfamily C
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NK Cell Lectin-Like Receptor Subfamily K
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Natural Cytotoxicity Triggering Receptor 1
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Natural Cytotoxicity Triggering Receptor 2
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Natural Cytotoxicity Triggering Receptor 3
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Interferon-gamma