Summary: Researchers investigate the different factors that affect our immune system and why some of us are more prone to diseases than others.
Source: Institute Pasteur.
Why do we respond differently to infections or vaccines? Why are some people allergic to pollen? These are still unanswered questions in biological and medical science. The Milieu Intérieur Laboratory of Excellence coordinated at the Institut Pasteur by CNRS research director, Dr. Lluis Quintana-Murci, has recently described immune variation on a large scale within the French population. To achieve this, the consortium studied an expansive collection of biological specimens from 1,000 French volunteers aged 20 to 69. This article provides an account of their work.
For many years, immunology, the branch of biology that examines our immune system, focused on dissecting the molecular mechanisms that control our physiological response to infections based on the assumption that this response does not differ among individuals. However, this premise has been challenged by recent studies suggesting that we are not all equally equipped to deal with pathogens. Our age, sex, infection history, and genetics can affect our immune system and make us more prone to disease. The task of identifying these factors that regulate our immune system has become the main challenge facing precision medicine, a proposed medical model aimed at offering patient treatments tailored to individual needs.
Some thirty scientists from several research centers thus joined forces to form the Milieu intérieur Laboratory of Excellence (or LabEx) coordinated at the Institut Pasteur by CNRS research director, Dr. Lluis Quintana-Murci with funding from the Investissements d’Avenir [Investing in the Future] program, with a view to describing immune variation on a large scale within the French population. This consortium gathered an expansive collection of biological specimens from 1,000 healthy donors (500 French men and 500 French women aged 20 to 69) recruited in Rennes. “The subjects’ blood, DNA, vaccination and medical history, and intestinal and nasal bacteria were collected, measured, and examined for this large-scale study”, explains Lluis Quintana-Murci. The first results from analysis of the entire cohort were recently published in PNAS on December 27, 2017 and in Nature Immunology on February 23, 2018.
Immune variation and differences in terms of sex and age
Using an ex vivo system, the researchers measured changes in immune gene expression in blood samples from the 1,000 donors when exposed to various viruses, bacteria, and fungi. At the same time, “we determined the molecular characteristics of the white blood cells, or leukocytes, in the donors’ blood with an unprecedented level of precision”, the CNRS researcher and study author Etienne Patin tells us. The two studies confirm that immune variation among individuals is largely due to differences in sex and age. “However, smoking and asymptomatic cytomegalovirus infection, which affects 35% of the population, also have a major impact on our blood cell composition. This may explain why smokers and people infected by this virus can be more prone to infection.”
Genetic variations and risk of disease
The researchers’ next task was to determine whether our genetics contribute to immune response variation among individuals. Surprisingly, “we identified hundreds of genetic variations which change the expression of molecules that play a key role in immune responses”, reports Lluis Quintana-Murci “some of which are associated with a higher risk of developing diseases such as pollen allergy, lupus erythematosus, and type 1 diabetes.” These results shed new light on the potential causes of these illnesses, which remain unclear.
The Milieu Intérieur Laboratory of Excellence (or Milieu intérieur LabEx) will now seek to determine whether our intestinal and nasal flora and epigenetics (temporary changes in our DNA) also contribute to immune variation. On a more general level, the extensive biobank developed for the purpose of this consortium will help identify disease risk factors, paving the way to precision medicine for infectious and autoimmune diseases.
[cbtabs][cbtab title=”MLA”]Institute Pasteur “The Factors that Most Affect Our Immune System.” NeuroscienceNews. NeuroscienceNews, 28 February 2018. < https://neurosciencenews.com/immune-system-activation-8578/>.[/cbtab][cbtab title=”APA”]Institute Pasteur (2018, February 28). The Factors that Most Affect Our Immune System. NeuroscienceNews. Retrieved February 28, 2018 from https://neurosciencenews.com/immune-system-activation-8578/[/cbtab][cbtab title=”Chicago”]Institute Pasteur “The Factors that Most Affect Our Immune System.” https://neurosciencenews.com/immune-system-activation-8578/ (accessed February 28, 2018).[/cbtab][/cbtabs]
Natural variation in the parameters of innate immune cells is preferentially driven by genetic factors
The quantification and characterization of circulating immune cells provide key indicators of human health and disease. To identify the relative effects of environmental and genetic factors on variation in the parameters of innate and adaptive immune cells in homeostatic conditions, we combined standardized flow cytometry of blood leukocytes and genome-wide DNA genotyping of 1,000 healthy, unrelated people of Western European ancestry. We found that smoking, together with age, sex and latent infection with cytomegalovirus, were the main non-genetic factors that affected variation in parameters of human immune cells. Genome-wide association studies of 166 immunophenotypes identified 15 loci that showed enrichment for disease-associated variants. Finally, we demonstrated that the parameters of innate cells were more strongly controlled by genetic variation than were those of adaptive cells, which were driven by mainly environmental exposure. Our data establish a resource that will generate new hypotheses in immunology and highlight the role of innate immunity in susceptibility to common autoimmune diseases.