Cargando…

Monkeypox Virus Infection of Rhesus Macaques Induces Massive Expansion of Natural Killer Cells but Suppresses Natural Killer Cell Functions

Natural killer (NK) cells play critical roles in innate immunity and in bridging innate and adaptive immune responses against viral infection. However, the response of NK cells to monkeypox virus (MPXV) infection is not well characterized. In this intravenous challenge study of MPXV infection in rhe...

Descripción completa

Detalles Bibliográficos
Autores principales: Song, Haifeng, Josleyn, Nicole, Janosko, Krisztina, Skinner, Jeff, Reeves, R. Keith, Cohen, Melanie, Jett, Catherine, Johnson, Reed, Blaney, Joseph E., Bollinger, Laura, Jennings, Gerald, Jahrling, Peter B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798392/
https://www.ncbi.nlm.nih.gov/pubmed/24147080
http://dx.doi.org/10.1371/journal.pone.0077804
_version_ 1782287772662366208
author Song, Haifeng
Josleyn, Nicole
Janosko, Krisztina
Skinner, Jeff
Reeves, R. Keith
Cohen, Melanie
Jett, Catherine
Johnson, Reed
Blaney, Joseph E.
Bollinger, Laura
Jennings, Gerald
Jahrling, Peter B.
author_facet Song, Haifeng
Josleyn, Nicole
Janosko, Krisztina
Skinner, Jeff
Reeves, R. Keith
Cohen, Melanie
Jett, Catherine
Johnson, Reed
Blaney, Joseph E.
Bollinger, Laura
Jennings, Gerald
Jahrling, Peter B.
author_sort Song, Haifeng
collection PubMed
description Natural killer (NK) cells play critical roles in innate immunity and in bridging innate and adaptive immune responses against viral infection. However, the response of NK cells to monkeypox virus (MPXV) infection is not well characterized. In this intravenous challenge study of MPXV infection in rhesus macaques (Macaca mulatta), we analyzed blood and lymph node NK cell changes in absolute cell numbers, cell proliferation, chemokine receptor expression, and cellular functions. Our results showed that the absolute number of total NK cells in the blood increased in response to MPXV infection at a magnitude of 23-fold, manifested by increases in CD56+, CD16+, CD16-CD56- double negative, and CD16+CD56+ double positive NK cell subsets. Similarly, the frequency and NK cell numbers in the lymph nodes also largely increased with the total NK cell number increasing 46.1-fold. NK cells both in the blood and lymph nodes massively proliferated in response to MPXV infection as measured by Ki67 expression. Chemokine receptor analysis revealed reduced expression of CXCR3, CCR7, and CCR6 on NK cells at early time points (days 2 and 4 after virus inoculation), followed by an increased expression of CXCR3 and CCR5 at later time points (days 7-8) of infection. In addition, MPXV infection impaired NK cell degranulation and ablated secretion of interferon-γ and tumor necrosis factor-α. Our data suggest a dynamic model by which NK cells respond to MPXV infection of rhesus macaques. Upon virus infection, NK cells proliferated robustly, resulting in massive increases in NK cell numbers. However, the migrating capacity of NK cells to tissues at early time points might be reduced, and the functions of cytotoxicity and cytokine secretion were largely compromised. Collectively, the data may explain, at least partially, the pathogenesis of MPXV infection in rhesus macaques.
format Online
Article
Text
id pubmed-3798392
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-37983922013-10-21 Monkeypox Virus Infection of Rhesus Macaques Induces Massive Expansion of Natural Killer Cells but Suppresses Natural Killer Cell Functions Song, Haifeng Josleyn, Nicole Janosko, Krisztina Skinner, Jeff Reeves, R. Keith Cohen, Melanie Jett, Catherine Johnson, Reed Blaney, Joseph E. Bollinger, Laura Jennings, Gerald Jahrling, Peter B. PLoS One Research Article Natural killer (NK) cells play critical roles in innate immunity and in bridging innate and adaptive immune responses against viral infection. However, the response of NK cells to monkeypox virus (MPXV) infection is not well characterized. In this intravenous challenge study of MPXV infection in rhesus macaques (Macaca mulatta), we analyzed blood and lymph node NK cell changes in absolute cell numbers, cell proliferation, chemokine receptor expression, and cellular functions. Our results showed that the absolute number of total NK cells in the blood increased in response to MPXV infection at a magnitude of 23-fold, manifested by increases in CD56+, CD16+, CD16-CD56- double negative, and CD16+CD56+ double positive NK cell subsets. Similarly, the frequency and NK cell numbers in the lymph nodes also largely increased with the total NK cell number increasing 46.1-fold. NK cells both in the blood and lymph nodes massively proliferated in response to MPXV infection as measured by Ki67 expression. Chemokine receptor analysis revealed reduced expression of CXCR3, CCR7, and CCR6 on NK cells at early time points (days 2 and 4 after virus inoculation), followed by an increased expression of CXCR3 and CCR5 at later time points (days 7-8) of infection. In addition, MPXV infection impaired NK cell degranulation and ablated secretion of interferon-γ and tumor necrosis factor-α. Our data suggest a dynamic model by which NK cells respond to MPXV infection of rhesus macaques. Upon virus infection, NK cells proliferated robustly, resulting in massive increases in NK cell numbers. However, the migrating capacity of NK cells to tissues at early time points might be reduced, and the functions of cytotoxicity and cytokine secretion were largely compromised. Collectively, the data may explain, at least partially, the pathogenesis of MPXV infection in rhesus macaques. Public Library of Science 2013-10-17 /pmc/articles/PMC3798392/ /pubmed/24147080 http://dx.doi.org/10.1371/journal.pone.0077804 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Song, Haifeng
Josleyn, Nicole
Janosko, Krisztina
Skinner, Jeff
Reeves, R. Keith
Cohen, Melanie
Jett, Catherine
Johnson, Reed
Blaney, Joseph E.
Bollinger, Laura
Jennings, Gerald
Jahrling, Peter B.
Monkeypox Virus Infection of Rhesus Macaques Induces Massive Expansion of Natural Killer Cells but Suppresses Natural Killer Cell Functions
title Monkeypox Virus Infection of Rhesus Macaques Induces Massive Expansion of Natural Killer Cells but Suppresses Natural Killer Cell Functions
title_full Monkeypox Virus Infection of Rhesus Macaques Induces Massive Expansion of Natural Killer Cells but Suppresses Natural Killer Cell Functions
title_fullStr Monkeypox Virus Infection of Rhesus Macaques Induces Massive Expansion of Natural Killer Cells but Suppresses Natural Killer Cell Functions
title_full_unstemmed Monkeypox Virus Infection of Rhesus Macaques Induces Massive Expansion of Natural Killer Cells but Suppresses Natural Killer Cell Functions
title_short Monkeypox Virus Infection of Rhesus Macaques Induces Massive Expansion of Natural Killer Cells but Suppresses Natural Killer Cell Functions
title_sort monkeypox virus infection of rhesus macaques induces massive expansion of natural killer cells but suppresses natural killer cell functions
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798392/
https://www.ncbi.nlm.nih.gov/pubmed/24147080
http://dx.doi.org/10.1371/journal.pone.0077804
work_keys_str_mv AT songhaifeng monkeypoxvirusinfectionofrhesusmacaquesinducesmassiveexpansionofnaturalkillercellsbutsuppressesnaturalkillercellfunctions
AT josleynnicole monkeypoxvirusinfectionofrhesusmacaquesinducesmassiveexpansionofnaturalkillercellsbutsuppressesnaturalkillercellfunctions
AT janoskokrisztina monkeypoxvirusinfectionofrhesusmacaquesinducesmassiveexpansionofnaturalkillercellsbutsuppressesnaturalkillercellfunctions
AT skinnerjeff monkeypoxvirusinfectionofrhesusmacaquesinducesmassiveexpansionofnaturalkillercellsbutsuppressesnaturalkillercellfunctions
AT reevesrkeith monkeypoxvirusinfectionofrhesusmacaquesinducesmassiveexpansionofnaturalkillercellsbutsuppressesnaturalkillercellfunctions
AT cohenmelanie monkeypoxvirusinfectionofrhesusmacaquesinducesmassiveexpansionofnaturalkillercellsbutsuppressesnaturalkillercellfunctions
AT jettcatherine monkeypoxvirusinfectionofrhesusmacaquesinducesmassiveexpansionofnaturalkillercellsbutsuppressesnaturalkillercellfunctions
AT johnsonreed monkeypoxvirusinfectionofrhesusmacaquesinducesmassiveexpansionofnaturalkillercellsbutsuppressesnaturalkillercellfunctions
AT blaneyjosephe monkeypoxvirusinfectionofrhesusmacaquesinducesmassiveexpansionofnaturalkillercellsbutsuppressesnaturalkillercellfunctions
AT bollingerlaura monkeypoxvirusinfectionofrhesusmacaquesinducesmassiveexpansionofnaturalkillercellsbutsuppressesnaturalkillercellfunctions
AT jenningsgerald monkeypoxvirusinfectionofrhesusmacaquesinducesmassiveexpansionofnaturalkillercellsbutsuppressesnaturalkillercellfunctions
AT jahrlingpeterb monkeypoxvirusinfectionofrhesusmacaquesinducesmassiveexpansionofnaturalkillercellsbutsuppressesnaturalkillercellfunctions