IFN-γ primes bone marrow neutrophils to acquire regulatory functions in severe viral respiratory infections
Neutrophil subsets endowed with regulatory/suppressive properties are widely regarded as deleterious immune cells that can jeopardize antitumoral response and/or antimicrobial resistance. Here, we describe a sizeable fraction of neutrophils characterized by the expression of programmed death-ligand 1 (PD-L1) in biological fluids of humans and mice with severe viral respiratory infections (VRI). Biological and transcriptomic approaches indicated that VRI-driven PD-L1<sup>+</sup> neutrophils are endowed with potent regulatory functions and reduced classical antimicrobial properties, as compared to their PD-L1<sup>-</sup> counterpart. VRI-induced regulatory PD-L1<sup>+</sup> neutrophils were generated remotely in the bone marrow in an IFN-γ-dependent manner and were quickly mobilized into the inflamed lungs where they fulfilled their maturation. Neutrophil depletion and PD-L1 blockade during experimental VRI resulted in higher mortality, increased local inflammation, and reduced expression of resolving factors. These findings suggest that PD-L1<sup>+</sup> neutrophils are important players in disease tolerance by mitigating local inflammation during severe VRI and that they may constitute relevant targets for future immune interventions.
Authors
- Roxane Lemoine (ORCID: https://orcid.org/0000-0002-9889-3614)
- Thomas Baranek (ORCID: https://orcid.org/0000-0002-5651-0937)
- Nathalie Winter (ORCID: https://orcid.org/0000-0003-0994-7834)
- Antoine Guillon (ORCID: https://orcid.org/0000-0002-4884-8620)
- Carolina de Amat Herbozo (ORCID: https://orcid.org/0000-0001-9216-6590)
- Qiaochu Lin (ORCID: https://orcid.org/0009-0003-9773-8465)
- Daphnée Soulard
- Mustapha Si‐Tahar (ORCID: https://orcid.org/0000-0002-5792-7742)
- Damien Sizaret (ORCID: https://orcid.org/0009-0009-8021-0342)
- François Trottein (ORCID: https://orcid.org/0000-0003-3373-1814)
- Valentin Sencio (ORCID: https://orcid.org/0000-0002-6379-4317)
- Christelle Faveeuw (ORCID: https://orcid.org/0000-0002-8373-3992)
- Benoit Briard (ORCID: https://orcid.org/0000-0002-1496-9408)
- Emilie Barsac
- Florent Creusat (ORCID: https://orcid.org/0009-0003-2258-5257)
- Youenn Jouan (ORCID: https://orcid.org/0000-0002-9844-814X)
- Guy Ilango
- Thierry Mallevaey (ORCID: https://orcid.org/0000-0001-8810-3482)
- Loïc Gonzalez (ORCID: https://orcid.org/0000-0002-5708-3332)
- Christophe Paget (ORCID: https://orcid.org/0000-0002-5374-5407)
- Antoine Hankard (ORCID: https://orcid.org/0000-0003-2305-7117)
- Chloé Boisseau
Institutions
- Université de Tours (FR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- University of Toronto (CA)
- Institut Pasteur de Lille (FR)
- Centre Hospitalier Universitaire de Lille (FR)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Centre Hospitalier Universitaire de Tours (FR)
- Center for Infection and Immunity of Lille (FR)
- Centre d'Étude des Pathologies Respiratoires (FR)
Publication Details
- Journal
- Science Advances
- Published
- 2024-10-11
- DOI
- https://doi.org/10.1126/sciadv.adn3257
- Citations
- 12
- Primary Topic
- Immune cells in cancer
- Type
- article
- Field-Weighted Citation Impact
- 2.89
Funders
- Agence Nationale de la Recherche
- Université François-Rabelais