Airway-delivered short-chain fatty acid acetate boosts antiviral immunity during rhinovirus infection
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved..
BACKGROUND: Microbiota are recognized to play a major role in regulation of immunity through release of immunomodulatory metabolites such as short-chain fatty acids (SCFAs). Rhinoviruses (RVs) induce upper respiratory tract illnesses and precipitate exacerbations of asthma and chronic obstructive pulmonary disease through poorly understood mechanisms. Local interactions between SCFAs and antiviral immune responses in the respiratory tract have not been previously investigated.
OBJECTIVE: We sought to investigate whether pulmonary metabolite manipulation through lung-delivered administration of SCFAs can modulate antiviral immunity to RV infection.
METHODS: We studied the effects of intranasal administration of the SCFAs acetate, butyrate, and propionate on basal expression of antiviral signatures, and of acetate in a mouse model of RV infection and in RV-infected lung epithelial cell lines. We additionally assessed the effects of acetate, butyrate, and propionate on RV infection in differentiated human primary bronchial epithelial cells.
RESULTS: Intranasal acetate administration induced basal upregulation of IFN-β, an effect not observed with other SCFAs. Butyrate induced RIG-I expression. Intranasal acetate treatment of mice increased interferon-stimulated gene and IFN-λ expression during RV infection and reduced lung virus loads at 8 hours postinfection. Acetate ameliorated virus-induced proinflammatory responses with attenuated pulmonary mucin and IL-6 expression observed at day 4 and 6 postinfection. This interferon-enhancing effect of acetate was confirmed in human bronchial and alveolar epithelial cell lines. In differentiated primary bronchial epithelial cells, butyrate treatment better modulated IFN-β and IFN-λ gene expression during RV infection.
CONCLUSIONS: SCFAs augment antiviral immunity and reduce virus load and proinflammatory responses during RV infection.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:151 |
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| Enthalten in: |
The Journal of allergy and clinical immunology - 151(2023), 2 vom: 01. Feb., Seite 447-457.e5 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Antunes, Krist Helen [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 07.02.2023 Date Revised 02.04.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jaci.2022.09.026 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM347313221 |
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| 100 | 1 | |a Antunes, Krist Helen |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Airway-delivered short-chain fatty acid acetate boosts antiviral immunity during rhinovirus infection |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 07.02.2023 | ||
| 500 | |a Date Revised 02.04.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: Microbiota are recognized to play a major role in regulation of immunity through release of immunomodulatory metabolites such as short-chain fatty acids (SCFAs). Rhinoviruses (RVs) induce upper respiratory tract illnesses and precipitate exacerbations of asthma and chronic obstructive pulmonary disease through poorly understood mechanisms. Local interactions between SCFAs and antiviral immune responses in the respiratory tract have not been previously investigated | ||
| 520 | |a OBJECTIVE: We sought to investigate whether pulmonary metabolite manipulation through lung-delivered administration of SCFAs can modulate antiviral immunity to RV infection | ||
| 520 | |a METHODS: We studied the effects of intranasal administration of the SCFAs acetate, butyrate, and propionate on basal expression of antiviral signatures, and of acetate in a mouse model of RV infection and in RV-infected lung epithelial cell lines. We additionally assessed the effects of acetate, butyrate, and propionate on RV infection in differentiated human primary bronchial epithelial cells | ||
| 520 | |a RESULTS: Intranasal acetate administration induced basal upregulation of IFN-β, an effect not observed with other SCFAs. Butyrate induced RIG-I expression. Intranasal acetate treatment of mice increased interferon-stimulated gene and IFN-λ expression during RV infection and reduced lung virus loads at 8 hours postinfection. Acetate ameliorated virus-induced proinflammatory responses with attenuated pulmonary mucin and IL-6 expression observed at day 4 and 6 postinfection. This interferon-enhancing effect of acetate was confirmed in human bronchial and alveolar epithelial cell lines. In differentiated primary bronchial epithelial cells, butyrate treatment better modulated IFN-β and IFN-λ gene expression during RV infection | ||
| 520 | |a CONCLUSIONS: SCFAs augment antiviral immunity and reduce virus load and proinflammatory responses during RV infection | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Human rhinovirus | |
| 650 | 4 | |a acetate | |
| 650 | 4 | |a antiviral response | |
| 650 | 4 | |a butyrate | |
| 650 | 4 | |a microbiota | |
| 650 | 4 | |a short-chain fatty acids | |
| 650 | 4 | |a type-I and type-III interferons | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Propionates |2 NLM | |
| 650 | 7 | |a Interferons |2 NLM | |
| 650 | 7 | |a 9008-11-1 |2 NLM | |
| 650 | 7 | |a Acetates |2 NLM | |
| 650 | 7 | |a Butyrates |2 NLM | |
| 700 | 1 | |a Singanayagam, Aran |e verfasserin |4 aut | |
| 700 | 1 | |a Williams, Lily |e verfasserin |4 aut | |
| 700 | 1 | |a Faiez, Tasnim Syakirah |e verfasserin |4 aut | |
| 700 | 1 | |a Farias, Ana |e verfasserin |4 aut | |
| 700 | 1 | |a Jackson, Millie M |e verfasserin |4 aut | |
| 700 | 1 | |a Faizi, Fatima K |e verfasserin |4 aut | |
| 700 | 1 | |a Aniscenko, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Kebadze, Tatiana |e verfasserin |4 aut | |
| 700 | 1 | |a Chander Veerati, Punnam |e verfasserin |4 aut | |
| 700 | 1 | |a Wood, Lisa |e verfasserin |4 aut | |
| 700 | 1 | |a Bartlett, Nathan W |e verfasserin |4 aut | |
| 700 | 1 | |a Duarte de Souza, Ana Paula |e verfasserin |4 aut | |
| 700 | 1 | |a Johnston, Sebastian L |e verfasserin |4 aut | |
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