Distinctive roles of age, sex, and genetics in shaping transcriptional variation of human immune responses to microbial challenges

Barbara Piasecka(Institut Pasteur), Darragh Duffy(Inserm), Alejandra Urrutia(Inserm), Hélène Quach(Centre National de la Recherche Scientifique), Étienne Patin(Centre National de la Recherche Scientifique), Céline Posseme(Institut Pasteur), Jacob Bergstedt(Institut Pasteur), Bruno Charbit(Institut Pasteur), Vincent Rouilly(Institut Pasteur), Cameron Ross MacPherson(Institut Pasteur), Milena Hasan(Institut Pasteur), Benoît Albaud(Institut Curie), David Gentien(Institut Curie), Jacques Fellay(SIB Swiss Institute of Bioinformatics), Matthew L. Albert(Inserm), Lluís Quintana‐Murci(Centre National de la Recherche Scientifique), Laurent Abel, Andrés Alcover, Hugues Aschard, Kalle Åström, Philippe Bousso, Pierre Bruhns, Ana Cumano, Darragh Duffy(Inserm), Caroline Demangel, Ludovic Deriano, James P. Di Santo, Françoise Dromer, Gérard Eberl, Jost Enninga, Jacques Fellay(SIB Swiss Institute of Bioinformatics), Magnus Fontes, António A. Freitas, Odile Gelpi, Ivo Gomperts-Boneca, Serge Herçberg, Olivier Lantz, Claude Leclerc, Hugo Mouquet, Étienne Patin(Centre National de la Recherche Scientifique), Sandra Pellegrini, Stanislas Pol, Antonio Raussel, Lars Rogge, Anavaj Sakuntabhai, Olivier Schwartz, Benno Schwikowski, Spencer Shorte, Vassili Soumelis, Frédéric Tangy, Éric Tartour, Antoine Toubert, Marie‐Noëlle Ungeheuer, Lluís Quintana‐Murci(Centre National de la Recherche Scientifique), Matthew L. Albert(Inserm)
Proceedings of the National Academy of Sciences
December 27, 2017
10.1073/pnas.1714765115
Cited by 238Open Access
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Abstract

Significance Identifying the drivers of the interindividual diversity of the human immune system is crucial to understand their consequences on immune-mediated diseases. By examining the transcriptional responses of 1,000 individuals to various microbial challenges, we show that age and sex influence the expression of many immune-related genes, but their effects are overall moderate, whereas genetic factors affect a smaller gene set but with a stronger effect. We identify numerous genetic variants that affect transcriptional variation on infection, many of which are associated with autoimmune or inflammatory disorders. These results enable additional exploration of the role of regulatory variants in the pathogenesis of immune-related diseases and improve our understanding of the respective effects of age, sex, and genetics on immune response variation.

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