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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 
Abstract : 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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03648209
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Submitted on : Thursday, April 21, 2022 - 11:40:20 AM
Last modification on : Friday, August 5, 2022 - 12:03:02 PM

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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, Nature Publishing Group: Open Access Hybrid Model Option B, 2022, ⟨10.1038/s41435-022-00169-5⟩. ⟨pasteur-03648209⟩

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