Dataset Information

Depletion but Activation of CD56^dimCD16⁺ NK Cells in Acute Infection with Severe Fever with Thrombocytopenia Syndrome Virus.

ABSTRACT: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality (12%-30%). The mechanism by which the SFTS bunyavirus (SFTSV) causes severe illness remains unclear. To evaluate the phenotypic and functional characteristics of the NK cell subsets in SFTS patients, twenty-nine SFTS patients were sequentially sampled from admission until recovery. Phenotypic and functional characteristics of NK cell subsets in circulating blood were analysed via flow cytometry. Then, correlations between NK cell subset frequencies and the SFTS index (SFTSI) were evaluated in all SFTS patients (15 mild, 14 severe) upon admission. The frequencies of CD56^dimCD16⁺ NK cells were greatly decreased in early SFTSV infection and were negatively correlated with disease severity. Additionally, higher Ki-67 and granzyme B expression and relatively lower NKG2A expression in CD56^dimCD16⁺ NK cells were observed in acute infection. Moreover, the effector function of CD56^dim NK cells was increased in the acute phase compared with the recovery phase in nine severe SFTS patients. Additionally, interleukin (IL)-15, interferon (IFN)-α, IL-18 and IFN-γ secretion was markedly increased during early infection. Collectively, despite depletion of CD56^dimCD16⁺ NK cells, activation and functional enhancement of CD56^dimCD16⁺ NK cells were still observed, suggesting their involvement in defence against early SFTSV infection.

SUBMITTER: Li M

PROVIDER: S-EPMC7736421 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Depletion but Activation of CD56<sup>dim</sup>CD16<sup>+</sup> NK Cells in Acute Infection with Severe Fever with Thrombocytopenia Syndrome Virus.

Li Mengmeng M Xiong Yan Y Li Mingyue M Zhang Wenjing W Liu Jia J Zhang Yanfang Y Xiong Shue S Zou Congcong C Liang Boyun B Lu Mengji M Yang Dongliang D Peng Cheng C Zheng Xin X

Virologica Sinica 20200519 5

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality (12%-30%). The mechanism by which the SFTS bunyavirus (SFTSV) causes severe illness remains unclear. To evaluate the phenotypic and functional characteristics of the NK cell subsets in SFTS patients, twenty-nine SFTS patients were sequentially sampled from admission until recovery. Phenotypic and functional characteristics of NK cell subsets in circulating blood were analysed via flow cytomet ...[more]

PMID: 32430872

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Project description:BackgroundHuman memory NK cells represent a heterogeneous CD56dim population that expands and persists in human cytomegalovirus (HCMV)-seropositive healthy individuals. They are characterized by the preferential, not fully overlapping, expression of NKG2C (activating receptor for HLA-E) and CD57 maturation marker, and by the lack of FcεRIγ adaptor chain. Hyperresponsiveness to Fcγ receptor IIIA (CD16) engagement represents the distinctive functional signature of memory NK cells. Although CD16 engagement was shown to acutely enhance glycolytic and oxidative pathways, its capability to induce a persisting metabolic reprogramming of human NK cells is poorly understood yet.ResultsHere, we describe the peculiar nutrient transporter expression pattern of FcεRIγ- memory NK cells, characterized by higher levels of CD98 neutral amino acid antiporter and CD71 transferrin receptor, and lower expression of GLUT1 glucose transporter, with respect to FcεRIγ+ conventional NK cells. Although CD16 engagement acutely enhances glycolytic and oxidative pathways, its capability to induce a persisting metabolic reprogramming of human NK cells is poorly understood yet. Our results firstly show that sustained CD16 engagement by contact with IgG-opsonized target cells induces the mTORC1-dependent upregulation of CD98 and CD71 nutrient receptors on CD56dim NK cells, in a transporter-specific fashion, that is finely tuned by cell-dependent (grade of functional maturation, and memory or conventional lineage) and stimulus-dependent (time length and cooperation with cytokines) factors. We also demonstrate that CD98 antiporter function is required for CD16-dependent IFN-γ production, and that enhanced CD98-mediated neutral amino acid uptake associates with heightened memory NK cell functional response.ConclusionCollectively, our work documents that CD16 engagement leads to a metabolic rewiring of human NK cells and suggests that a distinct nutrient transporter expression pattern may contribute to memory NK cell peculiar functional features.

Project description:Natural killer (NK) cells are innate cytotoxic and immunoregulatory lymphocytes that have a central role in anti-tumor immunity and play a critical role in mediating cellular immunity in advanced cancer immunotherapies, such as dendritic cell (DC) vaccines. Our group recently tested a novel recombinant adenovirus-transduced autologous DC-based vaccine that simultaneously induces T cell responses against three melanoma-associated antigens for advanced melanoma patients. Here, we examine the impact of this vaccine as well as the subsequent systemic delivery of high-dose interferon-α2b (HDI) on the circulatory NK cell profile in melanoma patients. At baseline, patient NK cells, particularly those isolated from high-risk patients with no measurable disease, showed altered distribution of CD56dim CD16+ and CD56dim CD16- NK cell subsets, as well as elevated serum levels of immune suppressive MICA, TN5E/CD73 and tactile/CD96, and perforin. Surprisingly, patient NK cells displayed a higher level of activation than those from healthy donors as measured by elevated CD69, NKp44 and CCR7 levels, and enhanced K562 killing. Elevated cytolytic ability strongly correlated with increased representation of CD56dim CD16+ NK cells and amplified CD69 expression on CD56dim CD16+ NK cells. While intradermal DC immunizations did not significantly impact circulatory NK cell activation and distribution profiles, subsequent HDI injections enhanced CD56bright CD16- NK cell numbers when compared to patients that did not receive HDI. Phenotypic analysis of tumor-infiltrating NK cells showed that CD56dim CD16- NK cells are the dominant subset in melanoma tumors. NanoString transcriptomic analysis of melanomas resected at baseline indicated that there was a trend of increased CD56dim NK cell gene signature expression in patients with better clinical response. These data indicate that melanoma patient blood NK cells display elevated activation levels, that intra-dermal DC immunizations did not effectively promote systemic NK cell responses, that systemic HDI administration can modulate NK cell subset distributions and suggest that CD56dim CD16- NK cells are a unique non-cytolytic subset in melanoma patients that may associate with better patient outcome.

Dataset Information

Depletion but Activation of CD56^dimCD16⁺ NK Cells in Acute Infection with Severe Fever with Thrombocytopenia Syndrome Virus.

Publications

Depletion but Activation of CD56<sup>dim</sup>CD16<sup>+</sup> NK Cells in Acute Infection with Severe Fever with Thrombocytopenia Syndrome Virus.

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Dataset Information

Depletion but Activation of CD56dimCD16+ NK Cells in Acute Infection with Severe Fever with Thrombocytopenia Syndrome Virus.

Publications

Depletion but Activation of CD56<sup>dim</sup>CD16<sup>+</sup> NK Cells in Acute Infection with Severe Fever with Thrombocytopenia Syndrome Virus.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Depletion but Activation of CD56^dimCD16⁺ NK Cells in Acute Infection with Severe Fever with Thrombocytopenia Syndrome Virus.