Airway-delivered short-chain fatty acid acetate boosts antiviral immunity during rhinovirus infection.

Autor: Antunes KH; Laboratory of Clinical and Experimental Immunology - Pontifical Catholic University of Rio Grande do Sul, Porto Alegre; National Heart and Lung Institute and, Department of Infectious Disease, Imperial College London, London., Singanayagam A; Centre for Molecular Bacteriology and Infection, Department of Infectious Disease, Imperial College London, London., Williams L; School of Biomedical Sciences and Pharmacy, The University of Newcastle, Newcastle., Faiez TS; Centre for Molecular Bacteriology and Infection, Department of Infectious Disease, Imperial College London, London., Farias A; National Heart and Lung Institute and, Department of Infectious Disease, Imperial College London, London., Jackson MM; Centre for Molecular Bacteriology and Infection, Department of Infectious Disease, Imperial College London, London., Faizi FK; Centre for Molecular Bacteriology and Infection, Department of Infectious Disease, Imperial College London, London., Aniscenko J; National Heart and Lung Institute and, Department of Infectious Disease, Imperial College London, London., Kebadze T; National Heart and Lung Institute and, Department of Infectious Disease, Imperial College London, London., Chander Veerati P; School of Biomedical Sciences and Pharmacy, The University of Newcastle, Newcastle., Wood L; School of Biomedical Sciences and Pharmacy, The University of Newcastle, Newcastle., Bartlett NW; National Heart and Lung Institute and, Department of Infectious Disease, Imperial College London, London; School of Biomedical Sciences and Pharmacy, The University of Newcastle, Newcastle., Duarte de Souza AP; Laboratory of Clinical and Experimental Immunology - Pontifical Catholic University of Rio Grande do Sul, Porto Alegre; National Heart and Lung Institute and, Department of Infectious Disease, Imperial College London, London. Electronic address: ana.duarte@pucrs.br., Johnston SL; National Heart and Lung Institute and, Department of Infectious Disease, Imperial College London, London; Asthma UK Centre in Allergic Mechanisms of Asthma, London. Electronic address: s.johnston@imperial.ac.uk.
Jazyk: angličtina
Zdroj: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2023 Feb; Vol. 151 (2), pp. 447-457.e5. Date of Electronic Publication: 2022 Oct 07.
DOI: 10.1016/j.jaci.2022.09.026
Abstrakt: 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.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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