An integrative approach for studying immunological variation in an aging population – The Milieu Intérieur follow-up study
Human immune responses vary across individuals due to both genetic and environmental factors. We previously established the Milieu Intérieur cohort to define boundaries of healthy immune variation and identify their determinants. To evaluate how immune responses change over time and test whether immune states can predict future disease, we conducted a 10-year follow-up of the cohort. Here we show widespread changes in humoral responses to pathogens over this period, including unexpected seroreversion of cytomegalovirus (CMV) status, despite a general age-related increase in CMV antibodies. We also investigated whether immune profiles at initial recruitment are associated with disease development a decade later. Strikingly, whole blood transcriptional responses to Staphylococcus aureus and Candida albicans stimulation were predictive of subsequent infectious disease. Collectively, the Milieu Intérieur longitudinal study represents a valuable resource for evaluating immune aging and may help identify predictors of adverse health outcomes.
Authors
- Violaine Saint‐André (ORCID: https://orcid.org/0000-0002-2162-0909)
- Antonio Rausell (ORCID: https://orcid.org/0000-0002-4832-6101)
- Anavaj Sakuntabhai (ORCID: https://orcid.org/0000-0001-9099-6937)
- Nadine Cerf–Bensussan (ORCID: https://orcid.org/0000-0003-0665-1245)
- M. Ménager
- Frédérique Michel (ORCID: https://orcid.org/0000-0002-3524-2232)
- Jost Enninga (ORCID: https://orcid.org/0000-0002-5218-349X)
- Rose Anne Kenny (ORCID: https://orcid.org/0000-0002-9336-8124)
- Gunilla Karlsson Hedestam
- Pierre Bruhns (ORCID: https://orcid.org/0000-0002-4709-8936)
- Frédéric Tangy (ORCID: https://orcid.org/0000-0002-5937-5654)
- Hugues Aschard (ORCID: https://orcid.org/0000-0002-7554-6783)
- Sandrine Fernandes Pellerin
- Slobodan Čulina (ORCID: https://orcid.org/0000-0001-6461-6953)
- Lars Rogge (ORCID: https://orcid.org/0000-0003-1262-9204)
- Vincent Rouilly (ORCID: https://orcid.org/0000-0003-3704-9310)
- Tom Dott
- Olivier Schwartz (ORCID: https://orcid.org/0000-0002-0729-1475)
- Caroline Demangel (ORCID: https://orcid.org/0000-0001-7848-586X)
- Benno Schwikowski (ORCID: https://orcid.org/0000-0001-5127-5619)
- Mélanie Briard (ORCID: https://orcid.org/0000-0001-6479-408X)
- Hugo Mouquet (ORCID: https://orcid.org/0000-0002-4230-610X)
- Florian Dubois (ORCID: https://orcid.org/0000-0002-7034-0866)
- Divya Unni
- Anthony Jaquaniello (ORCID: https://orcid.org/0009-0002-6585-0009)
- Ludovic Deriano (ORCID: https://orcid.org/0000-0002-9673-9525)
- Petter Brodin (ORCID: https://orcid.org/0000-0002-8103-0046)
- Marie‐Agnès Dillies
- Andrés Alcover (ORCID: https://orcid.org/0000-0002-9507-3450)
- Frédéric Rieux‐Laucat (ORCID: https://orcid.org/0000-0001-7858-7866)
- D Duffy
- Jacques Fellay (ORCID: https://orcid.org/0000-0002-8240-939X)
- Cliona O’Farrelly (ORCID: https://orcid.org/0000-0002-0616-2874)
- Chloe Albert-Vega
- Emma Bloch
- F. Rahal
- Magnus Fontes
- Etienne Patin
- Olivier Lantz
- James Di Santo
- Spencer Shorte
- Ana Cumano
- Nollaig Bourke
- Ivo Gomperts-Boneca
- Philippe Bousso
- Matthew L. Albert
- Serge Hercberg
- Michael White (ORCID: https://orcid.org/0000-0002-7472-4138)
- Milena Hasan (ORCID: https://orcid.org/0000-0002-0879-7099)
- Lluis Quintana-Murci
- Gérard Eberl
- Laurent Abel
- Christophe D’Enfert
- Christophe Zimmer
- Molly A. Ingersoll
- Etienne Villain (ORCID: https://orcid.org/0000-0001-9907-9094)
- Antoine Toubert
- Mathilde Touvier
- Marie-Noëlle Ungeheuer
Institutions
- Hôpital Necker-Enfants Malades (FR)
- Centre National de la Recherche Scientifique (FR)
- Institut de France (FR)
- University of Kaiserslautern (DE)
- Inserm (FR)
- Institut Pasteur (FR)
- Tokyo University of Science (JP)
- Collège de France (FR)
- Université Paris Cité (FR)
- Trinity College Dublin (IE)
- University of Würzburg (DE)
- Karolinska Institutet (SE)
- Roche (France) (FR)
- Immunité et Cancer (FR)
- Fondation HEC (FR)
- Institut Cochin (FR)
- Equipe de Recherche en Epidémiologie Nutritionnelle (FR)
- Institut des Maladies Génétiques Imagine (FR)
- Centre de Recherche Épidémiologie et Statistique (FR)
- Institut de recherche Saint-Louis (FR)
- Imperial College London (GB)
- École Polytechnique Fédérale de Lausanne (CH)
- Institut Curie (FR)
- Rockefeller University (US)
- University of Lausanne (CH)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-05-22
- DOI
- https://doi.org/10.1038/s41467-026-72910-x
- Primary Topic
- Cytomegalovirus and herpesvirus research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Agence Nationale de la Recherche