Immune monitoring

Oral

Impact of Age, Sex and Genetics on Transcriptional Immune Responses to Bacterial, Viral and Fungal Challenges

Friday, June 16
6:15 PM - 7:30 PM

Immune responses are highly variable between individuals and populations, with this variance mediated by many factors including age, sex, and genetics. To dissect how each of these factors contributes to differential immune responses we recruited 1,000 healthy donors as part of the Milieu Intereiur cohort that were equally stratified by age (20-70 years old) and sex (50:50). Whole blood from each donor was stimulated in a standardized approach with Escherichia coli, BCG, Stapholocus aureus, SEB, Candida albicans and Influenza virus and the transcriptomic response was analyzed by Nanostring gene expression arrays. We show that age affects gene expression in a stimuli specific manner, while the effect of sex is more common across conditions. Both age and sex contribute to the expression of many immune-related genes but at a low level, while in contrast, the genetic effects are much stronger but relevant to fewer genes. Genetic analysis identified hundreds of eQTLs, regulated in both cis and trans, for all stimuli induced responses. We confirm the presence of a TLR1 master regulator recently shown to be an important factor controlling variable immunity in European populations. Finally we integrated transcriptomic and cellular data sets in an integrative model to describe how age and sex mediated their effects through different immune cell populations. These results lay the foundations for new patient stratification strategies that consider age, sex, and genetics as impacting variable immune response outcomes.

Darragh Duffy

Institut Pasteur

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    Barbara Piasecka

    Institut Pasteur

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      Alejandra Urrutia

      Institut Pasteur

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        Helene Quach

        Institut Pasteur

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          Etienne Patin

          Institut Pasteur

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            Celine Posseme

            Institut Pasteur

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              Bruno Charbit

              Institut Pasteur

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                Vincent Rouilly

                Institut Pasteur

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                  Cameron MacPherson

                  Institut Pasteur

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                    Milena Hasan

                    Institut Pasteur

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                      Benoit Albaud

                      Institut Curie

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                        David Gentien

                        Institut Curie

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                          Jacques Fellay

                          EPFL

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                            Matthew Albert

                            Institut Pasteur

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                              Lluis Quintana Murci

                              Institut Pasteur

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                                Milieu Interieur

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                                  Impact of Age, Sex and Genetics on Transcriptional Immune Responses to Bacterial, Viral and Fungal Challenges



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