title: Expansion of 2B4+ natural killer (NK) cells and decrease in NKp46+ NK cells in response to influenza.
abstract: Several studies have highlighted the importance of murine natural killer (NK) cells in the control of influenza virus infection, notably through the natural cytotoxicity receptor NKp46. However, little is known about the involvement of NK cells in human influenza infection. Here, we show that upon in vitro exposure to influenza, NKp46 expression on NK cells decreases, whereas expression of 2B4, an activating receptor that can enhance natural cytotoxicity in synergy with NKp46, is up-regulated. Consistent with these observations, NKp46(dull) and 2B4(bright) NK cells had a higher functional activity in response to influenza than NK cells expressing high levels of NKp46 or low levels of 2B4, respectively. Importantly, we assessed whether the expression of these receptors was also modified in vivo in response to influenza antigens and showed that an increase in 2B4-expressing NK cells and a decrease in NKp46(+) NK cells occurred following intramuscular influenza vaccination. Altogether, our results further suggest that NKp46 may play an important role in the innate immune response to human influenza and reveal that exposure to influenza antigens is associated with a previously unrecognized increase in 2B4 expression that can impact NK cell activity against the virus.
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Boston, MA, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Jost
authors.forename: Jeff
authors.initials: J
authors.lastname: Reardon
authors.forename: Eric
authors.initials: E
authors.lastname: Peterson
authors.forename: Danielle
authors.initials: D
authors.lastname: Poole
authors.forename: Ronald
authors.initials: R
authors.lastname: Bosch
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000502:physiology; D007252:Influenza Vaccines / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000276:immunology* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D000071176:Signaling Lymphocytic Activation Molecule Family; D014611:Vaccination; D055815:Young Adult
chemical_list: D015703:Antigens, CD; C084093:CD244 protein, human; D007252:Influenza Vaccines; D052118:Lysosomal-Associated Membrane Protein 1; C112260:NCR1 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family; D007371:Interferon-gamma