Rev-erb-α antagonism in alveolar macrophages protects against pneumococcal infection in elderly mice
Summary: Circadian rhythms control the diurnal nature of many physiological, metabolic, and immune processes. We hypothesized that age-related impairments in circadian rhythms are associated with high susceptibility to bacterial respiratory tract infections. Our data show that the time-of-day differ...
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Elsevier
2025-02-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725000440 |
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| author | Fabiola Silva Angulo Claudine Vanessa Joseph Lou Delval Lucie Deruyter Séverine Heumel Marie Bicharel Patricia Brito Rodrigues Valentin Sencio Tom Bourguignon Marina Gomes Machado Marie Fourcot Stéphane Delhaye Sophie Salomé-Desnoulez Philippe Valet Serge Adnot Isabelle Wolowczuk Jean-Claude Sirard Muriel Pichavant Bart Staels Joel T. Haas Ruxandra Gref Jimmy Vandel Arnaud Machelart Hélène Duez Benoit Pourcet François Trottein |
| author_facet | Fabiola Silva Angulo Claudine Vanessa Joseph Lou Delval Lucie Deruyter Séverine Heumel Marie Bicharel Patricia Brito Rodrigues Valentin Sencio Tom Bourguignon Marina Gomes Machado Marie Fourcot Stéphane Delhaye Sophie Salomé-Desnoulez Philippe Valet Serge Adnot Isabelle Wolowczuk Jean-Claude Sirard Muriel Pichavant Bart Staels Joel T. Haas Ruxandra Gref Jimmy Vandel Arnaud Machelart Hélène Duez Benoit Pourcet François Trottein |
| author_sort | Fabiola Silva Angulo |
| collection | DOAJ |
| description | Summary: Circadian rhythms control the diurnal nature of many physiological, metabolic, and immune processes. We hypothesized that age-related impairments in circadian rhythms are associated with high susceptibility to bacterial respiratory tract infections. Our data show that the time-of-day difference in the control of Streptococcus pneumoniae infection is altered in elderly mice. A lung circadian transcriptome analysis revealed that aging alters the daily oscillations in the expression of a specific set of genes and that some pathways that are rhythmic in young-adult mice are non-rhythmic or time shifted in elderly mice. In particular, the circadian expression of the clock component Rev-erb-α and apelin/apelin receptor was altered in elderly mice. In young-adult mice, we discovered an interaction between Rev-erb-α and the apelinergic axis that controls host defenses against S. pneumoniae via alveolar macrophages. Pharmacological repression of Rev-erb-α in elderly mice resulted in greater resistance to pneumococcal infection. These data suggest the causative role of age-associated impairments in circadian rhythms on respiratory infections and have clinical relevance. |
| format | Article |
| id | doaj-art-daa291d32d904bd9bb15ab8fb98a8451 |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-daa291d32d904bd9bb15ab8fb98a84512025-02-05T04:31:49ZengElsevierCell Reports2211-12472025-02-01442115273Rev-erb-α antagonism in alveolar macrophages protects against pneumococcal infection in elderly miceFabiola Silva Angulo0Claudine Vanessa Joseph1Lou Delval2Lucie Deruyter3Séverine Heumel4Marie Bicharel5Patricia Brito Rodrigues6Valentin Sencio7Tom Bourguignon8Marina Gomes Machado9Marie Fourcot10Stéphane Delhaye11Sophie Salomé-Desnoulez12Philippe Valet13Serge Adnot14Isabelle Wolowczuk15Jean-Claude Sirard16Muriel Pichavant17Bart Staels18Joel T. Haas19Ruxandra Gref20Jimmy Vandel21Arnaud Machelart22Hélène Duez23Benoit Pourcet24François Trottein25University Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, 59000 Lille, FranceUniversity Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, 59000 Lille, FranceUniversity Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, 59000 Lille, FranceUniversity Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, 59000 Lille, FranceUniversity Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, 59000 Lille, FranceUniversity Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1011 - EGID, 59000 Lille, FranceUniversity Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, 59000 Lille, FranceUniversity Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, 59000 Lille, FranceUniversity Paris Saclay, CNRS, UMR 8214 - Institute of Molecular Sciences, 91400 Orsay, FranceUniversity Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, 59000 Lille, FranceUniversity Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, US 41 - UAR 2014 - PLBS, 59000 Lille, FranceUniversity Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1011 - EGID, 59000 Lille, FranceUniversity Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, US 41 - UAR 2014 - PLBS, 59000 Lille, FranceUniversity Paul Sabatier, University Toulouse, INSERM, CNRS, U1301 - UMR 5070 - Institut RESTORE, 31000 Toulouse, FranceUniversity Paris-Est Créteil, INSERM, U955, Institut Mondor de Recherche Biomédicale, 94010 Créteil, FranceUniversity Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, 59000 Lille, FranceUniversity Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, 59000 Lille, FranceUniversity Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, 59000 Lille, FranceUniversity Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1011 - EGID, 59000 Lille, FranceUniversity Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1011 - EGID, 59000 Lille, FranceUniversity Paris Saclay, CNRS, UMR 8214 - Institute of Molecular Sciences, 91400 Orsay, FranceUniversity Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, US 41 - UAR 2014 - PLBS, 59000 Lille, FranceUniversity Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, 59000 Lille, FranceUniversity Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1011 - EGID, 59000 Lille, France; Corresponding authorUniversity Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1011 - EGID, 59000 Lille, France; Corresponding authorUniversity Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, 59000 Lille, France; Corresponding authorSummary: Circadian rhythms control the diurnal nature of many physiological, metabolic, and immune processes. We hypothesized that age-related impairments in circadian rhythms are associated with high susceptibility to bacterial respiratory tract infections. Our data show that the time-of-day difference in the control of Streptococcus pneumoniae infection is altered in elderly mice. A lung circadian transcriptome analysis revealed that aging alters the daily oscillations in the expression of a specific set of genes and that some pathways that are rhythmic in young-adult mice are non-rhythmic or time shifted in elderly mice. In particular, the circadian expression of the clock component Rev-erb-α and apelin/apelin receptor was altered in elderly mice. In young-adult mice, we discovered an interaction between Rev-erb-α and the apelinergic axis that controls host defenses against S. pneumoniae via alveolar macrophages. Pharmacological repression of Rev-erb-α in elderly mice resulted in greater resistance to pneumococcal infection. These data suggest the causative role of age-associated impairments in circadian rhythms on respiratory infections and have clinical relevance.http://www.sciencedirect.com/science/article/pii/S2211124725000440CP: MicrobiologyCP: Immunology |
| spellingShingle | Fabiola Silva Angulo Claudine Vanessa Joseph Lou Delval Lucie Deruyter Séverine Heumel Marie Bicharel Patricia Brito Rodrigues Valentin Sencio Tom Bourguignon Marina Gomes Machado Marie Fourcot Stéphane Delhaye Sophie Salomé-Desnoulez Philippe Valet Serge Adnot Isabelle Wolowczuk Jean-Claude Sirard Muriel Pichavant Bart Staels Joel T. Haas Ruxandra Gref Jimmy Vandel Arnaud Machelart Hélène Duez Benoit Pourcet François Trottein Rev-erb-α antagonism in alveolar macrophages protects against pneumococcal infection in elderly mice Cell Reports CP: Microbiology CP: Immunology |
| title | Rev-erb-α antagonism in alveolar macrophages protects against pneumococcal infection in elderly mice |
| title_full | Rev-erb-α antagonism in alveolar macrophages protects against pneumococcal infection in elderly mice |
| title_fullStr | Rev-erb-α antagonism in alveolar macrophages protects against pneumococcal infection in elderly mice |
| title_full_unstemmed | Rev-erb-α antagonism in alveolar macrophages protects against pneumococcal infection in elderly mice |
| title_short | Rev-erb-α antagonism in alveolar macrophages protects against pneumococcal infection in elderly mice |
| title_sort | rev erb α antagonism in alveolar macrophages protects against pneumococcal infection in elderly mice |
| topic | CP: Microbiology CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725000440 |
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