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Coordinated Viral Control by Cytotoxic Lymphocytes Ensures Optimal Adaptive NK Cell Responses

Natural killer (NK) cells play a critical role in controlling viral infections, coordinating the response of innate and adaptive immune systems. They also possess certain features of adaptive lymphocytes, such as undergoing clonal proliferation. However, it is not known whether this adaptive NK cell...

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Autores principales: Diaz-Salazar, Carlos, Sun, Joseph C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532550/
https://www.ncbi.nlm.nih.gov/pubmed/32966792
http://dx.doi.org/10.1016/j.celrep.2020.108186
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author Diaz-Salazar, Carlos
Sun, Joseph C.
author_facet Diaz-Salazar, Carlos
Sun, Joseph C.
author_sort Diaz-Salazar, Carlos
collection PubMed
description Natural killer (NK) cells play a critical role in controlling viral infections, coordinating the response of innate and adaptive immune systems. They also possess certain features of adaptive lymphocytes, such as undergoing clonal proliferation. However, it is not known whether this adaptive NK cell response can be modulated by other lymphocytes during viral exposure. Here, we show that the clonal expansion of NK cells during mouse cytomegalovirus infection is severely blunted in the absence of cytotoxic CD8(+) T cells. This correlates with higher viral burden and an increased pro-inflammatory milieu, which maintains NK cells in a hyper-activated state. Antiviral therapy rescues NK cell expansion in the absence of CD8(+) T cells, suggesting that high viral loads have detrimental effects on adaptive NK cell responses. Altogether, our data support a mechanism whereby cytotoxic innate and adaptive lymphocytes cooperate to ensure viral clearance and the establishment of robust clonal NK cell responses.
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spelling pubmed-75325502020-10-03 Coordinated Viral Control by Cytotoxic Lymphocytes Ensures Optimal Adaptive NK Cell Responses Diaz-Salazar, Carlos Sun, Joseph C. Cell Rep Article Natural killer (NK) cells play a critical role in controlling viral infections, coordinating the response of innate and adaptive immune systems. They also possess certain features of adaptive lymphocytes, such as undergoing clonal proliferation. However, it is not known whether this adaptive NK cell response can be modulated by other lymphocytes during viral exposure. Here, we show that the clonal expansion of NK cells during mouse cytomegalovirus infection is severely blunted in the absence of cytotoxic CD8(+) T cells. This correlates with higher viral burden and an increased pro-inflammatory milieu, which maintains NK cells in a hyper-activated state. Antiviral therapy rescues NK cell expansion in the absence of CD8(+) T cells, suggesting that high viral loads have detrimental effects on adaptive NK cell responses. Altogether, our data support a mechanism whereby cytotoxic innate and adaptive lymphocytes cooperate to ensure viral clearance and the establishment of robust clonal NK cell responses. 2020-09-22 /pmc/articles/PMC7532550/ /pubmed/32966792 http://dx.doi.org/10.1016/j.celrep.2020.108186 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Diaz-Salazar, Carlos
Sun, Joseph C.
Coordinated Viral Control by Cytotoxic Lymphocytes Ensures Optimal Adaptive NK Cell Responses
title Coordinated Viral Control by Cytotoxic Lymphocytes Ensures Optimal Adaptive NK Cell Responses
title_full Coordinated Viral Control by Cytotoxic Lymphocytes Ensures Optimal Adaptive NK Cell Responses
title_fullStr Coordinated Viral Control by Cytotoxic Lymphocytes Ensures Optimal Adaptive NK Cell Responses
title_full_unstemmed Coordinated Viral Control by Cytotoxic Lymphocytes Ensures Optimal Adaptive NK Cell Responses
title_short Coordinated Viral Control by Cytotoxic Lymphocytes Ensures Optimal Adaptive NK Cell Responses
title_sort coordinated viral control by cytotoxic lymphocytes ensures optimal adaptive nk cell responses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532550/
https://www.ncbi.nlm.nih.gov/pubmed/32966792
http://dx.doi.org/10.1016/j.celrep.2020.108186
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