Mutually assured destruction: the cold war between viruses and natural killer cells

Ali, Ayad; Gyurova, Ivayla E; Waggoner, Stephen N.

doi:10.1016/j.coviro.2019.02.005

Cited by 22 publications

(24 citation statements)

References 146 publications

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“…Surveillance of cancerous cells and the regulation of the active immune system by NK cells have been investigated. 26,27 A 2017 comprehensive review summarized a number of studies about NK defects and cancer development and relapse. 28 Our findings suggest that NKD genes were associated with the recruitment of immune cells into TIMEs, and inherited defective genes in NK, NK T cells, and/or γδ T cells probably impaired communication between NK cells and other immune cells to block the recruitment of TILs.…”

Section: Discussionmentioning

confidence: 99%

Association of Germline Variants in Natural Killer Cells With Tumor Immune Microenvironment Subtypes, Tumor-Infiltrating Lymphocytes, Immunotherapy Response, Clinical Outcomes, and Cancer Risk

Xue

Zou

et al. 2019

JAMA Netw Open

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Key Points Question Are germline variants of natural killer (NK) cells associated with tumor immune microenvironment subtypes, cancer risk, prognosis, and immunotherapy? Findings This genetic association study analyzed functionally mutated genes in the germline genomes of 5883 patients with 13 common cancers and 4500 individuals with no cancer, finding that the number of functionally mutated genes in NK cell germlines was negatively associated with the abundance of tumor-infiltrating lymphocytes, clinical outcomes, and immunotherapy response but positively associated with cancer risk. Meaning Findings suggest that germline genetic variants in NK cells could help to identify individuals at risk of cancer and to improve existing immune checkpoint and chimeric antigen receptor–T cell therapies by adoptive transfer of healthy NK cells.

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Section: Discussionmentioning

confidence: 99%

Association of Germline Variants in Natural Killer Cells With Tumor Immune Microenvironment Subtypes, Tumor-Infiltrating Lymphocytes, Immunotherapy Response, Clinical Outcomes, and Cancer Risk

Xue

Zou

et al. 2019

JAMA Netw Open

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“…Natural killer (NK) cells mediate innate host defense against infection and tumors [1][2][3]. They develop predominantly from the common lymphoid progenitor [4].…”

Section: Introductionmentioning

confidence: 99%

Innate Cytokine Induced Early Release of IFNγ and CC Chemokines from Hypoxic Human NK Cells Is Independent of Glucose

Velásquez

Himmelhan

Kassner

et al. 2020

Cells

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Natural killer (NK) cells are among the first innate immune cells to arrive at sites of tissue inflammation and regulate the immune response to infection and tumors by the release of cytokines including interferon (IFN)γ. In vitro exposure to the innate cytokines interleukin 15 (IL-15) and IL-12/IL-18 enhances NK cell IFNγ production which, beyond 16 h of culture, was shown to depend on metabolic switching to glycolysis. NK effector responses are, however, rapid by comparison. Therefore, we sought to evaluate the importance of glycolysis for shorter-term IFNγ production, considering glucose deprivation and hypoxia as adverse tissue inflammation associated conditions. Treatments with IL-15 for 6 and 16 h were equally effective in priming early IFNγ production in human NK cells in response to secondary IL-12/IL-18 stimulation. Short-term priming was not associated with glycolytic switching but induced the release of IFNγ and, additionally, CCL3, CCL4 and CCL5 from both normoxic and hypoxic NK cells in an equally efficient and, unexpectedly, glucose independent manner. We conclude that release of IFNγ and CC chemokines in the early innate immune response is a metabolically autonomous NK effector program.

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“…6 B). As NK cells respond very early to virus infection ( Ali et al, 2019 ), we reason that this loss of NK cells is responsible for the increased virus replication in the liver of Il2rg KO hamsters at 4 days post challenge. However, the absence of NK cells was not complete: at 4 days post challenge with HAdV-C6, there was a ∼100-fold increase in the number of infiltrating NK cells in the liver ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Generation and characterization of an IL2RG knockout Syrian hamster model for XSCID and HAdV-C6 infection in immunocompromised patients

Bai

Liu

et al. 2020

Disease Models &Amp; Mechanisms

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Model animals are indispensable for the study of human diseases, and in general, of complex biological processes. The Syrian hamster is an important model animal for infectious diseases, behavioral science and metabolic science, for which more experimental tools are becoming available. Here, we describe the generation and characterization of an interleukin-2 receptor subunit gamma (Il2rg) knockout (KO) Syrian hamster strain. In humans, mutations in IL2RG can result in a total failure of T and natural killer (NK) lymphocyte development and nonfunctional B lymphocytes (X-linked severe combined immunodeficiency; XSCID). Therefore, we sought to develop a non-murine model to study XSCID and the infectious diseases associated with IL2RG deficiency. We demonstrated that the Il2rg KO hamsters have a lymphoid compartment that is greatly reduced in size and diversity, and is impaired in function. As a result of the defective adaptive immune response, Il2rg KO hamsters developed a more severe human adenovirus infection and cleared virus less efficiently than immune competent wild-type hamsters. Because of this enhanced virus replication, Il2rg KO hamsters developed more severe adenovirus-induced liver pathology than wild-type hamsters. This novel hamster strain will provide researchers with a new tool to investigate human XSCID and its related infections.

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Mutually assured destruction: the cold war between viruses and natural killer cells

Cited by 22 publications

References 146 publications

Association of Germline Variants in Natural Killer Cells With Tumor Immune Microenvironment Subtypes, Tumor-Infiltrating Lymphocytes, Immunotherapy Response, Clinical Outcomes, and Cancer Risk

Association of Germline Variants in Natural Killer Cells With Tumor Immune Microenvironment Subtypes, Tumor-Infiltrating Lymphocytes, Immunotherapy Response, Clinical Outcomes, and Cancer Risk

Innate Cytokine Induced Early Release of IFNγ and CC Chemokines from Hypoxic Human NK Cells Is Independent of Glucose

Generation and characterization of an IL2RG knockout Syrian hamster model for XSCID and HAdV-C6 infection in immunocompromised patients

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