Nature Communications

An integrative approach for studying immunological variation in an aging population – The Milieu Intérieur follow-up study

A Anthony Jaquaniello F Florian Dubois F Farah Rahal T Tom Dott S Slobodan Culina C Chloe Albert-Vega M Mélanie Briard V Vincent Rouilly E Etienne Villain V Violaine Saint-André D Divya Unni S Sandrine Fernandes Pellerin E Emma Bloch M Michael White M Milena Hasan L Lluis Quintana-Murci E Etienne Patin D Darragh Duffy L Laurent Abel (St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University) A Andres Alcover H Hugues Aschard P Philippe Bousso (Dynamics of Immune Responses Unit, Institut Pasteur, Université Paris Cité, INSERM U1223) N Nollaig Bourke P Petter Brodin P Pierre Bruhns N Nadine Cerf-Bensussan A Ana Cumano C Christophe d’Enfert (Institut Pasteur) C Caroline Demangel L Ludovic Deriano M Marie-Agnès Dillies J James Di Santo G Gérard Eberl J Jost Enninga J Jacques Fellay I Ivo Gomperts-Boneca G Gunilla Karlsson Hedestam S Serge Hercberg M Molly A. Ingersoll O Olivier Lantz R Rose Anne Kenny M Mickaël Ménager (Université de Paris Cité, Imagine Institute, Laboratory of Inflammatory Responses and Transcriptomic Networks in Diseases, Atip-Avenir Team, INSERM U1163) F Frédérique Michel H Hugo Mouquet C Cliona O’Farrelly A Antonio Rausell F Frédéric Rieux-Laucat (Université de Paris Cité, Imagine Institute Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163) L Lars Rogge M Magnus Fontes A Anavaj Sakuntabhai O Olivier Schwartz B Benno Schwikowski S Spencer Shorte F Frédéric Tangy A Antoine Toubert M Mathilde Touvier M Marie-Noëlle Ungeheuer C Christophe Zimmer M Matthew L. Albert

Abstract

Abstract 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.

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Article Details

Volume / Issue Vol. 17, Issue 1
Published May 22, 2026
ISSN 2041-1723
Publisher Nature Portfolio

Journal Info

Nature Communications

Nature Portfolio
ISSN: 2041-1723 Open Access Life Sciences

Authors (59)

A

Anthony Jaquaniello

F

Florian Dubois

F

Farah Rahal

T

Tom Dott

S

Slobodan Culina

C

Chloe Albert-Vega

M

Mélanie Briard

V

Vincent Rouilly

E

Etienne Villain

V

Violaine Saint-André

D

Divya Unni

S

Sandrine Fernandes Pellerin

E

Emma Bloch

M

Michael White

M

Milena Hasan

L

Lluis Quintana-Murci

E

Etienne Patin

D

Darragh Duffy

L

Laurent Abel

St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University

A

Andres Alcover

H

Hugues Aschard

P

Philippe Bousso

Dynamics of Immune Responses Unit, Institut Pasteur, Université Paris Cité, INSERM U1223

N

Nollaig Bourke

P

Petter Brodin

P

Pierre Bruhns

N

Nadine Cerf-Bensussan

A

Ana Cumano

C

Christophe d’Enfert

Institut Pasteur

C

Caroline Demangel

L

Ludovic Deriano

M

Marie-Agnès Dillies

J

James Di Santo

G

Gérard Eberl

J

Jost Enninga

J

Jacques Fellay

I

Ivo Gomperts-Boneca

G

Gunilla Karlsson Hedestam

S

Serge Hercberg

M

Molly A. Ingersoll

O

Olivier Lantz

R

Rose Anne Kenny

M

Mickaël Ménager

Université de Paris Cité, Imagine Institute, Laboratory of Inflammatory Responses and Transcriptomic Networks in Diseases, Atip-Avenir Team, INSERM U1163

F

Frédérique Michel

H

Hugo Mouquet

C

Cliona O’Farrelly

A

Antonio Rausell

F

Frédéric Rieux-Laucat

Université de Paris Cité, Imagine Institute Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163

L

Lars Rogge

M

Magnus Fontes

A

Anavaj Sakuntabhai

O

Olivier Schwartz

B

Benno Schwikowski

S

Spencer Shorte

F

Frédéric Tangy

A

Antoine Toubert

M

Mathilde Touvier

M

Marie-Noëlle Ungeheuer

C

Christophe Zimmer

M

Matthew L. Albert

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