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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 1 2 , Liyan Wen 3 , Hui-Ling Yen 4 , Ming Liu 5 , Yinping Liu 3 , Ooiean Teng 4 , Wing-Fung Wu 4 , Ke Ni 3 , Kowk-Tai Lam 3 , Chunyu Huang 3 , Jiashuang Yang 3 , Yu-Lung Lau 3 , Stanley Perlman 2 , Malik Peiris 6 , Wenwei Tu 1
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+NKG2A+ 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+NKG2A+ NK cells were recruited to infected lung and modulated viral clearance of virus and CD8+ 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+NKG2A+ 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.