tetano
Editor, Senior Moderator
J Virol
. 2021 Apr 7;JVI.00165-21.
doi: 10.1128/JVI.00165-21. Online ahead of print.
Phenotypic and functional characteristics of a novel influenza hemagglutinin-specific memory NK cell
Jian Zheng[SUP] 1 2 [/SUP], Liyan Wen[SUP] 3 [/SUP], Hui-Ling Yen[SUP] 4 [/SUP], Ming Liu[SUP] 5 [/SUP], Yinping Liu[SUP] 3 [/SUP], Ooiean Teng[SUP] 4 [/SUP], Wing-Fung Wu[SUP] 4 [/SUP], Ke Ni[SUP] 3 [/SUP], Kowk-Tai Lam[SUP] 3 [/SUP], Chunyu Huang[SUP] 3 [/SUP], Jiashuang Yang[SUP] 3 [/SUP], Yu-Lung Lau[SUP] 3 [/SUP], Stanley Perlman[SUP] 2 [/SUP], Malik Peiris[SUP] 6 [/SUP], Wenwei Tu[SUP] 1 [/SUP]
Affiliations
Abstract
Immune memory represents the most efficient defense against invasion and transmission of infectious pathogens. In contrast to memory T and B cells, the roles of innate immunity in recall responses remain inconclusive. In this study, we identified a novel mouse spleen NK cell subset expressing NKp46 and NKG2A induced by intranasal influenza virus infection. These memory NK cells specifically recognize N-linked glycosylation sites on influenza hemagglutinin (HA) protein. Different from memory-like NK cells reported previously, these NKp46[SUP]+[/SUP]NKG2A[SUP]+[/SUP] memory NK cells exhibited HA-specific silence of cytotoxicity but increase of IFN-? response against influenza virus-infected cells, which could be reversed by Pifithrin-?, a p53-HSP70 signaling inhibitor. During recall responses, splenic NKp46[SUP]+[/SUP]NKG2A[SUP]+[/SUP] NK cells were recruited to infected lung and modulated viral clearance of virus and CD8[SUP]+[/SUP] T cell distribution, resulting in improved clinical outcomes. This long-lived NK memory bridges innate and adaptive immune memory response and promotes the homeostasis of local environment during recall response.ImportanceIn this study, we demonstrate a novel HA-specific NKp46[SUP]+[/SUP]NKG2A[SUP]+[/SUP] NK cell subset induced by influenza A virus infection. These memory NK cells show virus-specific decreased cytotoxicity and increased IFN-? on re-encountering the same influenza virus antigen. In addition, they modulate host recall responses and CD8 T cell distribution, thus bridging the innate immune and adaptive immune responses during influenza virus infection.
. 2021 Apr 7;JVI.00165-21.
doi: 10.1128/JVI.00165-21. Online ahead of print.
Phenotypic and functional characteristics of a novel influenza hemagglutinin-specific memory NK cell
Jian Zheng[SUP] 1 2 [/SUP], Liyan Wen[SUP] 3 [/SUP], Hui-Ling Yen[SUP] 4 [/SUP], Ming Liu[SUP] 5 [/SUP], Yinping Liu[SUP] 3 [/SUP], Ooiean Teng[SUP] 4 [/SUP], Wing-Fung Wu[SUP] 4 [/SUP], Ke Ni[SUP] 3 [/SUP], Kowk-Tai Lam[SUP] 3 [/SUP], Chunyu Huang[SUP] 3 [/SUP], Jiashuang Yang[SUP] 3 [/SUP], Yu-Lung Lau[SUP] 3 [/SUP], Stanley Perlman[SUP] 2 [/SUP], Malik Peiris[SUP] 6 [/SUP], Wenwei Tu[SUP] 1 [/SUP]
Affiliations
- PMID: 33827945
- DOI: 10.1128/JVI.00165-21
Abstract
Immune memory represents the most efficient defense against invasion and transmission of infectious pathogens. In contrast to memory T and B cells, the roles of innate immunity in recall responses remain inconclusive. In this study, we identified a novel mouse spleen NK cell subset expressing NKp46 and NKG2A induced by intranasal influenza virus infection. These memory NK cells specifically recognize N-linked glycosylation sites on influenza hemagglutinin (HA) protein. Different from memory-like NK cells reported previously, these NKp46[SUP]+[/SUP]NKG2A[SUP]+[/SUP] memory NK cells exhibited HA-specific silence of cytotoxicity but increase of IFN-? response against influenza virus-infected cells, which could be reversed by Pifithrin-?, a p53-HSP70 signaling inhibitor. During recall responses, splenic NKp46[SUP]+[/SUP]NKG2A[SUP]+[/SUP] NK cells were recruited to infected lung and modulated viral clearance of virus and CD8[SUP]+[/SUP] T cell distribution, resulting in improved clinical outcomes. This long-lived NK memory bridges innate and adaptive immune memory response and promotes the homeostasis of local environment during recall response.ImportanceIn this study, we demonstrate a novel HA-specific NKp46[SUP]+[/SUP]NKG2A[SUP]+[/SUP] NK cell subset induced by influenza A virus infection. These memory NK cells show virus-specific decreased cytotoxicity and increased IFN-? on re-encountering the same influenza virus antigen. In addition, they modulate host recall responses and CD8 T cell distribution, thus bridging the innate immune and adaptive immune responses during influenza virus infection.