Utilisateur:Milieu2014/Brouillon

Une page de Wikipédia, l'encyclopédie libre.

The Milieu Intérieur Project[modifier | modifier le code]

The Milieu Intérieur Project is an ambitious population-based study coordinated by the Institut Pasteur, Paris. This program is part of a larger French Governmental Initiative called Investissement d'Avenir - Laboratoire d’Excellence (LabEx). This project is named after the French physiologist Claude Bernard’s concept of milieu intérieur and aims to establish the determinants of a healthy immune response by identifying factors (genetic and environmental) that contribute to the observed heterogeneity of immune responses. Restoring the ‘personal’ in medical care is a major challenge for medicine, and the driving vision of the project. This project is coordinated by Pr Matthew Albert (Institut Pasteur/Inserm U818) and Dr Lluis Quintana-Murci (Institut Pasteur/CNRS URA3012).

The Milieu Intérieur Project has a potential strong impact on public health, as the data generated will provide a foundation for defining perturbations in an individual’s immune responses, thus laying the foundation for personalized medicine.

Introduction[modifier | modifier le code]

Susceptibility to infections, disease severity, and response to medical therapies and vaccines are highly variable from one individual to another. The immune system is responsible for maintaining a healthy state and preventing infection in the majority of cases. However, dysfunction of the immune system can result in increased susceptibility to infections, inflammation, autoimmunity or even development of cancer in some individuals. Moreover, individual heterogeneity in the immune response can have an enormous impact on the likelihood to respond to therapy or the development of side effects secondary to vaccine administration. Because of the complexity of individual immune responses, as well as at the population level, it has not been possible thus far to define the genetic and environmental parameters that constitute a healthy immune system and its natural occurring variability. The aim of the Milieu Intérieur Project is to define how a healthy immune system responds to defined immune stimuli.

To achieve the stated goals, the Milieu Intérieur Project brings together high profile, renowned scientists and clinicians in the fields of immunology, infection biology, microbiology, virology, human genetics, evolutionary biology and systems biology.

Objectives[modifier | modifier le code]

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 responses, thus laying the foundation for personalized medicine.

The Milieu Interieur Consortium[modifier | modifier le code]

Institut Pasteur (Paris, France) is the host institution of the Milieu Intérieur Project. With researchers from five other French research organizations including Institut Curie, Paris-Diderot University, Paris-13 University, INSERM and CNRS, the Consortium Milieu Intérieur regroups research groups whose multi-disciplinary expertise will permit to establish the parameters that characterize the immune system of healthy individuals.

The Milieu Intérieur multi-disciplinary Consortium federates researchers and clinicians across several disciplines, and through the integration of cutting-edge technology in the fields of immunology, genomics, molecular biology, virology, infectiology, and bioinformatics.

Public Health Impact[modifier | modifier le code]

A unique and personalized approach to health care management for each patient? If this was still an abstract concept a few years ago, advances in technology are making this concept a reality. The promise of personalized medicine is to design the most suitable treatment for each individual patient (at the right time). This concept takes into account the genetics of the person, her predisposition to develop a particular disease and her environmental exposures, in order to prevent the development of disease or tailor specific treatments. However, there are still many challenges to introduce the concept of personalized medicine in the clinic. Efforts to restore the ‘personal’ in medical care are the current challenge, and the driving vision of the Milieu Intérieur Project.

Given the role of inflammation, and host immunity in disease pathogenesis, the Milieu Intérieur 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

Achievements[modifier | modifier le code]

The Milieu Intérieur Project is divided into four phases. All milestones of phase 1 (foundation phase) were successfully achieved: validation of immune stimulation assays in whole blood for 27 stimulus conditions, using TruCulture® technology; design and approval of a clinical protocol for the recruitment of 1,000 healthy individuals stratified by age and gender; development of ten 8-color cytometry panels; building of a sample tracking solution; automation for sample handling and analysis pilot studies on all protocols. In phase 2 (consolidation phase) of the project, the Milieu Intérieur Project has recruited the 1,000 healthy donors and constituted a sample bank of whole blood culture supernatants and RNA, feces, nasal swabs and punch biopsies across the whole cohort. The cytometry and proteomic data have been generated and are being analyzed. Genomic DNA from all healthy donors has been extracted and sent for whole-genome genotyping. This means that data is in hand to start phase 3 (discovery-based phase). Phase 4 (association studies in disease settings) will propose comparison studies in disease states.


1,000 healthy donors[modifier | modifier le code]

A total of 1,000 healthy volunteers (1:1 sex ratio; stratified across five-decades of life) were recruited between September 17th, 2012 to August 8th, 2013 as a reference cohort, with the objective to identify genotype -to- immune phenotype correlations in healthy persons, and serving also as a control for future disease cohort studies. The study was approved by the CPP – Ouest 6 on June 13th, 2012 and by ANSM on June 22nd, 2012 and is sponsored by Institut Pasteur (Pasteur ID-RCB Number: 2012-A00238-35). Whole blood was collected for immunologic phenotyping, functional immune stimulation and preparation of DNA for genomic analysis. Fecal samples and nasal swabs were obtained for metagenomic studies. Punch biopsies of the skin were taken and primary fibroblast lines were generated for future mechanistic investigation. This well-defined cohort and sample collection strategy has established the foundation for defining variability of the human immune responsiveness.


Monitoring the functional immune response[modifier | modifier le code]

One innovative aspect of the project relies on the use of a whole-blood assay device - TruCulture® - which preserves physiological cellular interactions and provides a reproducible means of assessing the complexities of innate and adaptive human immune responses.

A total of 32 different immune stimuli conditions have been selected and whole blood assays have been validated, standardized and produced.

References[modifier | modifier le code]

Defining the boundaries of a healthy immune response: functional analysis of immune responsiveness using standardized whole blood stimulation systems. D. Duffy, V. Rouilly, V. Libri, M. Hasan, B. Beitz, M. David, A. Urrutia, A. Bisiaux, S. LaBrie, A. Dubois, I. Gomperts-Boneca, C. Delval, S. Thomas, L. Rogge, M. Schmolz, L. Quintana-Murci, M. Albert for The Milieu Intérieur Consortium. Immunity. March, 20th, 2014.

External links[modifier | modifier le code]

Milieu InterieurInstitut Pasteur