Temperature sensitivity of bat antibodies links metabolic state of bats with antigen-recognition diversity

• Published in: Nature Communications
• Main Authors: Toshkova, Nia, Zhelyzkova, Violeta, Reyes-Ruiz, Alejandra, Haerens, Eline, de Castro Deus, Marina, Lacombe, Robin, Lecerf, Maxime, Gonzalez, Gaelle, Jouvenet, Nolwenn, Planchais, Cyril, Dimitrov, Jordan D.
• Other Authors: Bulgarian Academy of Sciences (BAS), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre National de la Recherche Scientifique (CNRS), Virologie UMR1161 (VIRO), École nationale vétérinaire d'Alfort (ENVA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Normandie, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Signalisation antivirale - Virus sensing and signaling, Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Immunologie humorale - Humoral Immunology, Institut Pasteur Paris (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), The experimental work was supported by a grant from European Research Council (Project CoBABATI ERC-StG-678905), awarded to J.D.D. Fieldwork funding was provided by the Bulgarian National Science Fund (project KP-06-N51/9 “Caves as a reservoir for novel and reoccurring zoonoses—ecological monitoring and metagenomic analysis in real-time”). N.T. was funded by а Ph.D. Fellowship from Karoll Knowledge Foundation and a stipend from the French Institute, Bulgaria. V.Z. was supported by a stipend from the French Institute, Bulgaria. A.R.R. is recipient of a fellowship from an Innovative Training Network (ITN) funded by the European Union’s Horizon 2020 Programme under grant agreement No 859974, project EDUC8., European Project: 678905,H2020-EU.1.1., ERC-StG-2015,CoBABATI(2016), European Project: 859974,H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions,EDUC8(2020)
• Format: Article in Journal/Newspaper
• Language: English
• Published: HAL CCSD 2024
• Subjects: Animal physiology; Antibodies; Inflammation; Molecular evolution; [SDV]Life Sciences [q-bio]; Lacroix; Pasteur; Sheffield; Nyctalus noctula
• Online Access: https://pasteur.hal.science/pasteur-04675437; https://pasteur.hal.science/pasteur-04675437/document; https://pasteur.hal.science/pasteur-04675437/file/Temperature%20sensitivity%20of%20bat%20antibodies%20links%20metabolic%20state%20of%20bats%20with%20antigen-recognition%20diversity%20-%2041467_2024_Article_50316.pdf; https://doi.org/10.1038/s41467-024-50316-x

We would like to express our gratitude to the volunteers who assisted us in the field: Boris Petrov, Petar Velkov, Katrin Dimitrova, Kaloyana Koseva, Kristin Meshinska, and Stela-Teodora Trendafilova. Our heartfelt thanks go to Dr Lubka Roumenina, and Dr Sebastien Lacroix-Desmazes (both from Centre de Recherche des Cordeliers, Paris, France) for their insightful feedback on our ideas and their unwavering intellectual support throughout this study. We thank Dr Hugo Mouquet, Dr Vishu Kumar Aimanianda (both from Institute Pasteur, Paris, France) and Dr Stephane Mesnage, (University of Sheffield, UK) for providing us with some important material (pathogen proteins, antibodies, and plasmids). We also thank Pr. J. Pikula and Dr. V. Kovácová (Department of Ecology and Diseases of Zoo Animals, Game, Fish and Bees, University of Veterinary and Pharmaceutical Sciences Brno) for sharing the MmNep cells. International audience The bat immune system features multiple unique properties such as dampened inflammatory responses and increased tissue protection, explaining their long lifespan and tolerance to viral infections. Here, we demonstrated that body temperature fluctuations corresponding to different physiological states in bats exert a large impact on their antibody repertoires. At elevated temperatures typical for flight, IgG from the bat species Myotis myotis and Nyctalus noctula show elevated antigen binding strength and diversity, recognizing both pathogen-derived antigens and autoantigens. The opposite is observed at temperatures reflecting inactive physiological states. IgG antibodies of human and other mammals, or antibodies of birds do not appear to behave in a similar way. Importantly, diversification of bat antibody specificities results in preferential recognition of damaged endothelial and epithelial cells, indicating an anti-inflammatory function. The temperature-sensitivity of bat antibodies is mediated by the variable regions of immunoglobulin molecules. Additionally, we uncover specific molecular ...