PD-L1+ plasma cells suppress T lymphocyte responses in patients with sepsis and mouse sepsis models
Morgane Gossez, Clara Vigneron, Alexandra Vandermoeten, Margot Lepage, Louise Courcol, Rémy Coudereau, Helena Païdassi, Laurent Jallades, Jonathan Lopez, Khalil Kandara, Marine Ortillon, Marine Mommert, Astrid Fabri, Estelle Peronnet, Clémence Grosjean, Marielle Buisson, Anne‐Claire Lukaszewicz, Thomas Rimmelé, Laurent Argaud, Martin Cour, REALISM study group, Sophie Arnal, Caroline Augris-Mathieu, Frédérique Bayle, Liana Caruso, Charles-Éric Ber, Asma Ben-Amor, Anne-Sophie Bellocq, Farida Benatir, Anne Bertin-Maghit, M. Bertin‐Maghit, A. Boibieux, Yves Bouffard, Jean‐Christophe Cejka, Valérie Cerro, Jullien Crozon-Clauzel, Julien Davidson, Sophie Debord-Peguet, Benjamin Delwarde, Robert Deléat-Besson, Claire Delsuc, Bertrand Dévigne, Laure Fayolle-Pivot, Alexandre Faure, Bernard Floccard, Julie Gatel, Charline Genin, Thibaut Girardot, Arnaud Grégoire, Baptiste Hengy, Laetitia Huriaux, Catherine Jadaud, Alain Lepape, Véronique Leray, Anne‐Claire Lukaszewicz, Guillaume Marcotte, Olivier Martin, Marie Matray, Delphine Maucort‐Boulch, Pascal Meuret, Céline Monard, Florent Moriceau, Guillaume Monneret, Nathalie Panel, N. Rahali, Thomas Rimmelé, Cyrille Truc, Thomas Uberti, Hélène Vallin, S. Tissot, Abbès Zadam, Sophie Blein, Karen Brengel‐Pesce, Elisabeth Cerrato, Valérie Cheynet, Emmanuelle Gallet-Gorius, Audrey Guichard, Camille Jourdan, Natacha Koenig, François Mallet, Boris Meunier, Virginie Moucadel, Guy Oriol, Alexandre Pachot, Claire Schrevel, Olivier Tabone, Julien Textoris, Javier Yugueros Marcos, Jérémie Becker, Frédéric Bequet, Yacine Bounab, Florian Brajon, Bertrand Canard, Muriel Collus, Nathalie Garçon, Irène Gorse, Cyril Guyard, Fabien Lavocat, Philippe Leissner, Karen Seashore Louis
Abstract
Abstract Sepsis, a leading cause of death in intensive care units, is associated with immune alterations that increase the patients’ risk of secondary infections and mortality, so better understandings of the pathophysiology of sepsis-induced immunosuppression is essential for the development of therapeutic strategies. In a murine model of sepsis that recapitulates immune alterations observed in patients, here we demonstrate that PD-L1 + CD44 + B220 Low CD138 + IgM + regulatory plasma cells are induced in spleen and regulate ex vivo proliferation and IFNɣ secretion induced by stimulation of T splenocytes. This effect is mediated both by cell-cell contact through increased PD-L1 expression on plasma cells and by production of a soluble factor. These observations are recapitulated in three cohorts of critically ill patients with bacterial and viral sepsis in association with increased mortality. Our findings thus reveal the function of regulatory plasma cells in the pathophysiology of sepsis-induced immune alterations, and present a potential therapeutic target for improving immune cell function impaired by sepsis.