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

被引:30
作者
Antunes, Krist Helen [1 ,2 ]
Singanayagam, Aran [3 ]
Williams, Lily [4 ]
Faiez, Tasnim Syakirah [3 ]
Farias, Ana [2 ]
Jackson, Millie M. [3 ]
Faizi, Fatima K. [3 ]
Aniscenko, Julia [2 ]
Kebadze, Tatiana [2 ]
Veerati, Punnam Chander [4 ]
Wood, Lisa [4 ]
Bartlett, Nathan W. [2 ,4 ]
de Souza, Ana Paula Duarte [1 ,2 ,6 ]
Johnston, Sebastian L. [2 ,5 ,7 ]
机构
[1] Pontificia Univ Catolica Rio Grande do Sul, Lab Clin & Expt Immunol, Porto Alegre, Brazil
[2] Imperial Coll London, Natl Heart & Lung Inst, London, England
[3] Imperial Coll London, Ctr Mol Bacteriol & Infect, Dept Infect Dis, London, England
[4] Univ Newcastle, Sch Biomed Sci & Pharm, Newcastle, England
[5] Asthma UK Ctr Allerg Mech Asthma, London, England
[6] Pontificia Univ Catolica Rio Grande do Sul, Sch Hlth & Life Sci, BR-90610000 Porto Alegre, RS, Brazil
[7] Imperial Coll London, Natl Heart & Lung Inst, London W2 1PG, England
关键词
Human rhinovirus; type-I and type-III interferons; ace-tate; antiviral response; butyrate; short-chain fatty acids; microbiota; DIETARY FIBER; DISEASE; EXACERBATION; CELLS; MODEL;
D O I
10.1016/j.jaci.2022.09.026
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
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-13, an effect not observed with other SCFAs. Butyrate induced RIG-I expression. Intranasal acetate treatment of mice increased interferon-stimulated gene and IFN-l 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-13 and IFN-l gene expression during RV infection. Conclusions: SCFAs augment antiviral immunity and reduce virus load and proinflammatory responses during RV infection. (J Allergy Clin Immunol 2023;151:447-57.)
引用
收藏
页码:447 / +
页数:16
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