Respiratory Syncytial Virus Infects Primary Neonatal and Adult Natural Killer Cells and Affects Their Antiviral Effector Function
© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America..
BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of severe acute lower respiratory tract infections in infants. Natural killer (NK) cells are important antiviral effector cells that likely encounter RSV in the presence of virus-specific (maternal) antibodies. As NK cells potentially contribute to immunopathology, we investigated whether RSV affects their antiviral effector functions.
METHODS: We assessed the phenotype and functionality of primary neonatal and adult NK cells by flow cytometry after stimulation with RSV or RSV-antibody complexes.
RESULTS: We demonstrate for the first time that RSV infects neonatal and adult NK cells in vitro. Preincubation of virus with subneutralizing concentrations of RSV-specific antibodies significantly increased the percentage of infected NK cells. Upon infection, NK cells were significantly more prone to produce interferon-γ, while secretion of the cytotoxicity molecule perforin was not enhanced.
CONCLUSIONS: Our findings suggest that (antibody-enhanced) RSV infection of NK cells induces a proinflammatory rather than a cytotoxic response, which may contribute to immunopathology. Considering that most RSV vaccines currently being developed aim at inducing (maternal) antibodies, these results highlight the importance of understanding the interactions between innate effector cells and virus-specific antibodies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:219 |
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| Enthalten in: |
The Journal of infectious diseases - 219(2019), 5 vom: 15. Feb., Seite 723-733 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
van Erp, Elisabeth A [VerfasserIn] |
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| Links: |
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| Themen: |
126465-35-8 |
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| Anmerkungen: |
Date Completed 12.11.2019 Date Revised 09.03.2020 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/infdis/jiy566 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM288883357 |
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| 245 | 1 | 0 | |a Respiratory Syncytial Virus Infects Primary Neonatal and Adult Natural Killer Cells and Affects Their Antiviral Effector Function |
| 264 | 1 | |c 2019 | |
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| 500 | |a Date Completed 12.11.2019 | ||
| 500 | |a Date Revised 09.03.2020 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. | ||
| 520 | |a BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of severe acute lower respiratory tract infections in infants. Natural killer (NK) cells are important antiviral effector cells that likely encounter RSV in the presence of virus-specific (maternal) antibodies. As NK cells potentially contribute to immunopathology, we investigated whether RSV affects their antiviral effector functions | ||
| 520 | |a METHODS: We assessed the phenotype and functionality of primary neonatal and adult NK cells by flow cytometry after stimulation with RSV or RSV-antibody complexes | ||
| 520 | |a RESULTS: We demonstrate for the first time that RSV infects neonatal and adult NK cells in vitro. Preincubation of virus with subneutralizing concentrations of RSV-specific antibodies significantly increased the percentage of infected NK cells. Upon infection, NK cells were significantly more prone to produce interferon-γ, while secretion of the cytotoxicity molecule perforin was not enhanced | ||
| 520 | |a CONCLUSIONS: Our findings suggest that (antibody-enhanced) RSV infection of NK cells induces a proinflammatory rather than a cytotoxic response, which may contribute to immunopathology. Considering that most RSV vaccines currently being developed aim at inducing (maternal) antibodies, these results highlight the importance of understanding the interactions between innate effector cells and virus-specific antibodies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 4 | |a NK cells | |
| 650 | 4 | |a RSV | |
| 650 | 4 | |a antibody | |
| 650 | 4 | |a interferon-γ | |
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| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a Perforin |2 NLM | |
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| 700 | 1 | |a Feyaerts, Dorien |e verfasserin |4 aut | |
| 700 | 1 | |a Duijst, Maxime |e verfasserin |4 aut | |
| 700 | 1 | |a Mulder, H Lie |e verfasserin |4 aut | |
| 700 | 1 | |a Wicht, Oliver |e verfasserin |4 aut | |
| 700 | 1 | |a Luytjes, Willem |e verfasserin |4 aut | |
| 700 | 1 | |a Ferwerda, Gerben |e verfasserin |4 aut | |
| 700 | 1 | |a van Kasteren, Puck B |e verfasserin |4 aut | |
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