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

• DOI: 10.1073/pnas.1714765115
• Publication Date: 2017-12-27T19:36:25Z
• Authors: Barbara Piasecka; Darragh Duffy; Alejandra Urrutia; Hélène Quach; Etienne Patin; Céline Posseme; Jacob Bergstedt; Bruno Charbit; Vincent Rouilly; Cameron R. MacPhe...; Milena Hasan; Benoit Albaud; David Gentien; Jacques Fellay; Matthew L. Albert; Lluis Quintana-Murci; ; Laurent Abel; Andres Alcover; Hugues Aschard; Kalle Aström; Philippe Bousso; Pierre Bruhns; Ana Cumano; Darragh Duffy; Caroline Demangel; Ludovic Deriano; James Di Santo; Françoise Dromer; Gérard Eberl; Jost Enninga; Jacques Fellay; Magnus Fontes; Antonio Freitas; Odile Gelpi; Ivo Gomperts-Boneca; Serge Hercberg; Olivier Lantz; Claude Leclerc; Hugo Mouquet; Etienne Patin; Sandra Pellegrini; Stanislas Pol; Antonio Raussel; Lars Rogge; Anavaj Sakuntabhai; Olivier Schwartz; Benno Schwikowski; Spencer Shorte; Vassili Soumelis; Frédéric Tangy; Eric Tartour; Antoine Toubert; Marie-Noëlle Unge...; Lluis Quintana-Murci; Matthew L. Albert
• Keywords: Adult; Male; Aging; [SDV.IMM] Life Sciences [q-bio]/Immunology; Genotype; Quantitative Trait Loci; Cohort Studies; Enterotoxins; Young Adult; 03 medical and health sciences; sex; Humans; genetics; Aged; 0303 health sciences; Bacteria; Fungi; Genetic Variation; Middle Aged; Adult; Aged; Aging; Bacteria/immunology; Cohort Studies; Enterotoxins/immunology; Female; Fungi/immunology; Gene Expression Regulation/immunology; Genetic Variation; Genotype; Humans; Influenza A virus/immunology; Male; Middle Aged; Quantitative Trait Loci; Young Adult; age; gene expression; genetics; human immune variation; sex; 3. Good health; human immune variation; age; PNAS Plus; Gene Expression Regulation; Influenza A virus; gene expression; [SDV.IMM]Life Sciences [q-bio]/Immunology; Female

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.