The Milieu Interieur Project

Coordinated by Matthew Albert and Lluis Quintana-Murci


A systems approach to understanding the Immune System 
Genetic & Environmental Determinants of Immune Phenotype Variance

The Milieu Interieur project is an ambitious population based study supported by the French National Ministry of Research and being coordinated by the Institut Pasteur, Paris.

Inspired by the French physiologist Claude Bernard’s concept of le milieu intérieur (the environment within), the project aims to establish the determinants of a healthy immune response. By defining the genetic and environmental factors controlling immune responsiveness, it will for the first time be possible to harness our immune phenotype variance for purposes of prognosis, diagnosis and theragnosis.

Rationale for the Milieu Interieur Project

Susceptibility to infection and inflammation, severity of disease and response to medical therapies or vaccines all show high inter-individual variability. We are finally in a position to evaluate this variable response in a reproducible and systematic manner. By combining simple to use measures of functional immune responsiveness with genetic, epigenetic and meta-genomic profiling, we will establish an unprecedented dataset that will unlock the secret for patient stratification.

Objectives of the Milieu Interieur Project

The objectives of the Milieu Interieur project are to:

•    Establish a deep understanding of immune variance;
•    Define how immune phenotypic variation is genetically controlled and;
•    Ascertain the role of the microbiota in regulating immune programs.

These efforts will establish parameters for stratifying individuals within a population, thus making it possible to glean meaningful interpretation from measurements of stress-induced host response. In achieving this goal, the project will provide a foundation for defining perturbations in an individual’s immune system responses, thus laying the foundation for personalized medicine.

Monitoring the functional immune response

To achieve the stated goals the Milieu Interieur project brings together internationally renowned scientists from Institut Pasteur in the fields of immunology, human genetics, microbiology and systems biology – creating a bridge to key industrial partners. The innovative aspect of the project relies on the use of a whole-blood assay device, which preserves physiological cellular interaction - but even more importantly, it provides a reproducible means of assessing the complexities of innate and adaptive human immune responses.

Immune stimuli will be selected and whole blood assays will be validated and standardized. Selected stimuli will allow researchers to describe immune signatures for defined adjuvants, immune modulators, hormones, cytokines or pro-biotic agents. These data will be analyzed for induced expression Quantitative Trait Locus (eQTL) mapping thus providing the genetic determinants of immune variance. Additional correlations will be performed based on defined enterotype classification.

Public health impact of the Milieu Interieur project

From a public health perspective, the Milieu Interieur project will provide cheap and easy to use point-of-care applications for use in stratifying individuals. Given the role of inflammation and host immunity in disease pathogenesis, the Milieu Interieur project is poised to impact:

•    Therapeutic and prophylactic vaccination of healthy donors (especially with respect to adjuvant choice for an aging population);
•    Optimizing treatment response while minimizing side effects;
•    Development and implementation of pro- and pre-biotics.  



LabEx Project - Milieu Interieur