Phenotypic and Functional Characteristics of a Novel Influenza Virus Hemagglutinin-Specific Memory NK Cell

Zheng, Jian; Wen, Liyan; Yen, Hui-Ling; Liu, Ming; Liu, Yinping; Teng, Ooiean; Wu, Weiju; Ni, Ke; Lam, Kowk-Tai; Huang, Chunyu; Yang, Jiashuang; Lau, Yu Lung; Perlman, Stanley; Peiris, Malik; Tu, Wenwei

doi:10.1128/jvi.00165-21

Cited by 12 publications

(8 citation statements)

References 71 publications

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“…9 These studies led to the understanding that NK cells have several functions previously solely attributed to cells of the adaptive immune system (i.e., clonal expansion, contraction, longevity of primed cells, and enhanced secondary effector responses), thereby challenging the existing dogma of NK cells functioning solely as innate killer cells (reviewed in 10,11 ). Although the plurality of studies on NK cell memory have been conducted in the context of CMV infections, NK cell memory was first observed in response to stimulation with haptens 12 and has also been noted in response to other viral infections [13][14][15][16] and cytokines. 17 Given the fact that naïve NK cells are unable to persist for more than 14 days, and the transcriptome of memory NK cells is closely related to naïve NK cells, 18 epigenetic processes were proposed as critical regulators of NK cell memory formation and survival.…”

Section: N V I T E D R E V I E W No Time To Die: Epigenetic Regulatio...mentioning

confidence: 99%

No time to die: Epigenetic regulation of natural killer cell survival

Hermans,

O'Sullivan

2024

Immunological Reviews

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SummaryNK cells are short‐lived innate lymphocytes that can mediate antigen‐independent responses to infection and cancer. However, studies from the past two decades have shown that NK cells can acquire transcriptional and epigenetic modifications during inflammation that result in increased survival and lifespan. These findings blur the lines between the innate and adaptive arms of the immune system, and suggest that the homeostatic mechanisms that govern the persistence of innate immune cells are malleable. Indeed, recent studies have shown that NK cells undergo continuous and strictly regulated adaptations controlling their survival during development, tissue residency, and following inflammation. In this review, we summarize our current understanding of the critical factors regulating NK cell survival throughout their lifespan, with a specific emphasis on the epigenetic modifications that regulate the survival of NK cells in various contexts. A precise understanding of the molecular mechanisms that govern NK cell survival will be important to enhance therapies for cancer and infectious diseases.

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Section: N V I T E D R E V I E W No Time To Die: Epigenetic Regulatio...mentioning

confidence: 99%

No time to die: Epigenetic regulation of natural killer cell survival

Hermans,

O'Sullivan

2024

Immunological Reviews

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“…Influenza-specific memory NK-cells have recently been identified in mice. 114 Future studies will likely establish the exact role and importance of innate memory in respiratory viral infections.…”

Section: Part Iv: Memorymentioning

confidence: 99%

The Immune Response to Respiratory Viruses: From Start to Memory

Reijnders

Schuurman

Poll

2021

Semin Respir Crit Care Med

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Biomedical research has long strived to improve our understanding of the immune response to respiratory viral infections, an effort that has become all the more important as we live through the consequences of a pandemic. The disease course of these infections is shaped in large part by the actions of various cells of the innate and adaptive immune systems. While these cells are crucial in clearing viral pathogens and establishing long-term immunity, their effector mechanisms may also escalate into excessive, tissue-destructive inflammation detrimental to the host. In this review, we describe the breadth of the immune response to infection with respiratory viruses such as influenza and respiratory syncytial virus. Throughout, we focus on the host rather than the pathogen and try to describe shared patterns in the host response to different viruses. We start with the local cells of the airways, onto the recruitment and activation of innate and adaptive immune cells, followed by the establishment of local and systemic memory cells key in protection against reinfection. We end by exploring how respiratory viral infections can predispose to bacterial superinfection.

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“…The interest in harnessing NK cell functions for vaccine design and therapeutic interventions against these pathogens has markedly increased in recent years, largely driven by a series of observations indicating that subpopulations of NK cells, called memory or adaptive NK cells, manifest multiple forms of durable adaptive capabilities ( 4 ). This includes reports of true antigen-specific memory NK cells that can mediate recall responses against infectious agents, including HIV ( 5 – 7 ) and influenza ( 5 , 8 – 10 ). Adaptive NK cell subsets have been associated with protective effects in people living with HIV (PLWH) ( 11 – 14 ), and exposure to influenza antigens induces protective influenza-specific memory NK cells in mouse models ( 5 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

Antigen-specific memory NK cell responses against HIV and influenza use the NKG2/HLA-E axis

Jost,

Lucar,

Lee

et al. 2023

Sci. Immunol.

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Multiple studies have broadened the roles of natural killer (NK) cells functioning as purely innate lymphocytes by demonstrating that they are capable of putative antigen-specific immunological memory against multiple infectious agents including HIV-1 and influenza. However, the mechanisms underlying antigen specificity remain unknown. Here, we demonstrate that antigen-specific human NK cell memory develops upon exposure to both HIV and influenza, unified by a conserved and epitope-specific targetable mechanism largely dependent on the activating CD94/NKG2C receptor and its ligand HLA-E. We validated the permanent acquisition of antigen specificity by individual memory NK cells by single-cell cloning. We identified elevated expression of KLRG1, α4β7, and NKG2C as biomarkers of antigen-specific NK cell memory through complex immunophenotyping. Last, we uncovered individual HLA-E–restricted peptides that may constitute the dominant NK cell response in HIV-1– and influenza-infected persons in vivo. Our findings clarify the mechanisms contributing to antigen-specific memory NK cell responses and suggest that they could be potentially targeted therapeutically for vaccines or other therapeutic interventions.

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Phenotypic and Functional Characteristics of a Novel Influenza Virus Hemagglutinin-Specific Memory NK Cell

Cited by 12 publications

References 71 publications

No time to die: Epigenetic regulation of natural killer cell survival

No time to die: Epigenetic regulation of natural killer cell survival

The Immune Response to Respiratory Viruses: From Start to Memory

Antigen-specific memory NK cell responses against HIV and influenza use the NKG2/HLA-E axis

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