Rhesus negative males have an enhanced IFNγ-mediated immune response to influenza A virus

Jamie A. Sugrue (1) , Megan Smith (1) , Celine Posseme (2) , Bruno Charbit (3) , Nollaig M. Bourke (1) , Darragh Duffy (2, 3) , Cliona O'Farrelly (1) , Laurent Abel (4) , Andres Alcover (1) , Hugues Aschard (1) , Philippe Bousso (1) , Petter Brodin (5) , Pierre Bruhns (6) , Nadine Cerf-Bensussan (6) , Ana Cumano (7) , Christophe D'Enfert (7) , Ludovic Deriano (7) , Marie-Agnès Dillies (7) , James Di Santo (7) , Françoise Dromer (7) , Gérard Eberl (7) , Jost Enninga (7) , Jacques Fellay (7) , Ivo Gomperts-Boneca (5) , Milena Hasan (5) , Gunilla Karlsson Hedestam (5) , Serge Hercberg (8) , Molly A. Ingersoll (9) , Olivier Lantz (9) , Rose Anne Kenny (1) , Mickaël Ménager (6) , Hugo Mouquet (1) , Cliona O’farrelly (1) , Etienne Patin (6) , Sandra Pellegrini (6) , Antonio Rausell (6) , Frédéric Rieux-Laucat (6) , Lars Rogge (10) , Magnus Fontes (10) , Anavaj Sakuntabhai (11) , Olivier Schwartz (11) , Benno Schwikowski (11) , Spencer Shorte (11) , Frédéric Tangy (11) , Antoine Toubert (11) , Mathilde Touvier (8) , Marie-Noëlle Ungeheuer (12) , Christophe Zimmer (12) , Matthew L. Albert (12) , Lluis Quintana-Murci (13)

1 Trinity College Dublin
2 Immunologie Translationnelle - Translational Immunology lab
3 UTechS CB - Cytometrie et Biomarqueurs – Cytometry and Biomarkers
4 CHU Necker - Enfants Malades [AP-HP]
5 Karolinska Institutet [Stockholm]
6 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
7 EPFL - Ecole Polytechnique Fédérale de Lausanne
8 UP13 - Université Paris 13
9 Institut Curie [Paris]
10 Institut ROCHE [Boulogne-Billancourt]
11 AP-HP - Hopital Saint-Louis [AP-HP]
12 Insitro [San Francisco]
13 IP - Institut Pasteur [Paris]

The Rhesus D antigen (RhD) has been associated with susceptibility to several viral infections. Reports suggest that RhD-negative individuals are better protected against infectious diseases and have overall better health. However, potential mechanisms contributing to these associations have not yet been defined. Here, we used transcriptomic and genomic data from the Milieu Interieur cohort of 1000 healthy individuals to explore the effect of Rhesus status on the immune response. We used the rs590787 SNP in the RHD gene to classify the 1000 donors as either RhD-positive or -negative. Whole blood was stimulated with LPS, polyIC, and the live influenza A virus and the NanoString human immunology panel of 560 genes used to assess donor immune response and to investigate sex-specific effects. Using regression analysis, we observed no significant differences in responses to polyIC or LPS between RhD-positive and -negative individuals. However, upon sex-specific analysis, we observed over 40 differentially expressed genes (DEGs) between RhD-positive ( n = 384) and RhD-negative males ( n = 75) after influenza virus stimulation. Interestingly these Rhesus-associated differences were not seen in females. Further investigation, using gene set enrichment analysis, revealed enhanced IFNγ signalling in RhD-negative males. This amplified IFNγ signalling axis may explain the increased viral resistance previously described in RhD-negative individuals.

Domains: Immunology

Jamie A. Sugrue, Megan Smith, Celine Posseme, Bruno Charbit, Nollaig M. Bourke, et al.. Rhesus negative males have an enhanced IFNγ-mediated immune response to influenza A virus. Genes and Immunity, 2022, ⟨10.1038/s41435-022-00169-5⟩. ⟨pasteur-03648209⟩