Integrated analysis of whole blood oxylipin and cytokine responses after bacterial, viral, and T cell stimulation reveals new immune networks

Etienne Villain; Aurélie Chanson; Malwina Mainka; Nadja Kampschulte; Pauline Le Faouder; Justine Bertrand-Michel; Marion Brandolini-Bulon; Bruno Charbit; Munyaradzi Musvosvi; Nicole Bilek; Thomas J Scriba; Lluis Quintana-Murci; Nils Helge Schebb; Darragh Duffy; Cécile Gladine; Milieu Interieur Consortium

doi:10.1016/j.isci.2023.107422

Integrated analysis of whole blood oxylipin and cytokine responses after bacterial, viral, and T cell stimulation reveals new immune networks

iScience. 2023 Jul 18;26(8):107422. doi: 10.1016/j.isci.2023.107422. eCollection 2023 Aug 18.

Authors

Etienne Villain¹, Aurélie Chanson², Malwina Mainka³, Nadja Kampschulte³, Pauline Le Faouder⁴, Justine Bertrand-Michel⁴, Marion Brandolini-Bulon^{2

5}, Bruno Charbit⁶, Munyaradzi Musvosvi⁷, Nicole Bilek⁷, Thomas J Scriba⁷, Lluis Quintana-Murci^{8

9}, Nils Helge Schebb³, Darragh Duffy^{1

6}, Cécile Gladine²; Milieu Interieur Consortium

Collaborators

Milieu Interieur Consortium:
Laurent Abel, Andres Alcover, Hugues Aschard, Philippe Bousso, Nollaig Bourke, Petter Brodin, Pierre Bruhns, Nadine Cerf-Bensussan, Ana Cumano, Christophe D'Enfert, Ludovic Deriano, Marie-Agnès Dillies, James Di Santo, Gérard Eberl, Jost Enninga, Jacques Fellay, Ivo Gomperts-Boneca, Milena Hasan, Gunilla Karlsson Hedestam, Serge Hercberg, Molly A Ingersoll, Olivier Lantz, Rose Anne Kenny, Mickaël Ménager, Hugo Mouquet, Cliona O'Farrelly, Etienne Patin, Sandra Pellegrini, Antonio Rausell, Frédéric Rieux-Laucat, Lars Rogge, Magnus Fontes, Anavaj Sakuntabhai, Olivier Schwartz, Benno Schwikowski, Spencer Shorte, Frédéric Tangy, Antoine Toubert, Mathilde Touvier, Marie-Noëlle Ungeheuer, Christophe Zimmer, Matthew L Albert, Darragh Duffy, Lluis Quintana-Murci

Affiliations

¹ Institut Pasteur, Université Paris Cité, Translational Immunology Unit, Paris, France.
² Université Clermont Auvergne, INRAE, UNH, Clermont-Ferrand, France.
³ Chair of Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Wuppertal, Germany.
⁴ MetaToul, MetaboHUB, Inserm/UPS UMR 1048-I2MC, Institut des Maladies Métaboliques et Cardiovasculaires, 31400 Toulouse, France.
⁵ Université Clermont Auvergne, INRAE, UNH, Plateforme D'Exploration Du Métabolisme, MetaboHUB Clermont, Clermont-Ferrand, France.
⁶ Institut Pasteur, Université Paris Cité, CBUTechS, Paris, France.
⁷ South African Tuberculosis Vaccine Initiative (SATVI), Division of Immunology, Department of Pathology and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
⁸ Institut Pasteur, Université Paris Cité, CNRS UMR2000, Human Evolutionary Genetics Unit, Paris, France.
⁹ Collège de France, 75005 Paris, France.

Abstract

Oxylipins are major immunomodulating mediators, yet studies of inflammation focus mainly on cytokines. Here, using a standardized whole-blood stimulation system, we characterized the oxylipin-driven inflammatory responses to various stimuli and their relationships with cytokine responses. We performed a pilot study in 25 healthy individuals using 6 different stimuli: 2 bacterial stimuli (LPS and live BCG), 2 viral stimuli (vaccine-grade poly I:C and live H1N1 attenuated influenza), an enterotoxin superantigen and a Null control. All stimuli induced a strong production of oxylipins but most importantly, bacterial, viral, and T cell immune responses show distinct oxylipin signatures. Integration of the oxylipin and cytokine responses for each condition revealed new immune networks improving our understanding of inflammation regulation. Finally, the oxylipin responses and oxylipin-cytokine networks were compared in patients with active tuberculosis or with latent infection. This revealed different responses to BCG but not LPS stimulation highlighting new regulatory pathways for further investigations.

Keywords: Immune response; Immunology; Microbiology.