Rev-erb-α antagonism in alveolar macrophages protects against pneumococcal infection in elderly mice
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.
Authors
- Bart Staels (ORCID: https://orcid.org/0000-0002-3784-1503)
- Christie George Joseph (ORCID: https://orcid.org/0009-0000-6040-7687)
- Muriel Pichavant (ORCID: https://orcid.org/0000-0002-1315-4397)
- Serge Adnot (ORCID: https://orcid.org/0000-0001-5666-3063)
- Arnaud Machelart (ORCID: https://orcid.org/0000-0002-4444-0011)
- Hélène Duez (ORCID: https://orcid.org/0000-0002-4130-7987)
- Ruxandra Gref (ORCID: https://orcid.org/0000-0002-7869-0908)
- Séverine Heumel (ORCID: https://orcid.org/0000-0001-8649-5814)
- Jimmy Vandel (ORCID: https://orcid.org/0000-0003-0189-0220)
- Lou Delval (ORCID: https://orcid.org/0000-0002-3854-4439)
- François Trottein (ORCID: https://orcid.org/0000-0003-3373-1814)
- Tom Bourguignon (ORCID: https://orcid.org/0000-0001-5356-4000)
- Valentin Sencio (ORCID: https://orcid.org/0000-0002-6379-4317)
- Joel T. Haas (ORCID: https://orcid.org/0000-0002-0028-5988)
- Marie Fourcot
- Stéphane Delhaye (ORCID: https://orcid.org/0000-0001-9438-6730)
- Isabelle Wolowczuk (ORCID: https://orcid.org/0000-0001-6692-6904)
- Benoît Pourcet (ORCID: https://orcid.org/0000-0002-6758-5467)
- Jean‐Claude Sirard (ORCID: https://orcid.org/0000-0001-9854-4652)
- Sophie Salomé‐Desnoulez (ORCID: https://orcid.org/0000-0002-2637-8576)
- Lucie Deruyter
- Paula Rodrigues (ORCID: https://orcid.org/0000-0002-3789-2730)
- Fabiola Silva (ORCID: https://orcid.org/0000-0002-3564-8849)
- Marina Machado (ORCID: https://orcid.org/0000-0002-8996-613X)
- Philippe Valet (ORCID: https://orcid.org/0000-0001-6520-7393)
- Marie Bicharel
Institutions
- Centre National de la Recherche Scientifique (FR)
- Université Toulouse III - Paul Sabatier (FR)
- Inserm (FR)
- Université Paris-Est Créteil (FR)
- Université Paris-Saclay (FR)
- Institut Pasteur de Lille (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- Institut des Sciences Moléculaires (FR)
- Institut des Neurosciences Paris-Saclay (FR)
- Institut des Sciences des Plantes de Paris Saclay (FR)
- Center for Infection and Immunity of Lille (FR)
- Institut Mondor de Recherche Biomédicale (FR)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-02-01
- DOI
- https://doi.org/10.1016/j.celrep.2025.115273
- Citations
- 5
- Primary Topic
- Tryptophan and brain disorders
- Type
- article
- Field-Weighted Citation Impact
- 2.89
Funders
- European Genomic Institute for Diabetes
- European Commission
- Agence Nationale de la Recherche
- Conseil Régional Hauts-de-France