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Bacterial sensing via neuronal Nod2 regulates appetite and body temperature

Authors :
Ilana Gabanyi
Gabriel Lepousez
Richard Wheeler
Alba Vieites-Prado
Antoine Nissant
Sébastien Wagner
Carine Moigneu
Sophie Dulauroy
Samia Hicham
Bernadette Polomack
Florine Verny
Philip Rosenstiel
Nicolas Renier
Ivo Gomperts Boneca
Gérard Eberl
Pierre-Marie Lledo
Perception et Mémoire / Perception and Memory
Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
Microenvironnement et Immunité - Microenvironment and Immunity
Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
Toxines bactériennes - Bacterial Toxins
Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047)
Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Institut du Cerveau = Paris Brain Institute (ICM)
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP]
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047)
Christian-Albrechts University of Kiel
Institutional support was provided by Institut Pasteur, CNRS, and Inserm. Also supported by Pasteur-Roux postdoctoral fellowships from the Institut Pasteur (I.G.), a Human Frontier Science Program fellowship (I.G.), Agence Nationale de la Recherche grant ANR-16-CE15-0021 (I.G.B., P.-M.L., G.C. and G.E.), DFG CRC1182 project C2 (P.R.), and life insurance company 'AG2R-La-Mondiale' (P.-M.L.).
We thank S. Saha, E. de Launoit, and T. Topilko for their help in conducting and/or analyzing experiments
G. Chevalier for his preliminary work on Nod2GFP mice
and D. Mucida and G. M. Silva for their insightful discussions and critical reading and editing of the manuscript. We would also like to thank P. Campagne from the Hub of Bioinformatics and Biostatistics of the Institut Pasteur for his advice on the statistical tests used in this work and the members of the Animalerie Centrale of the Institut Pasteur for maintenance and care of the mice used in this work. We also thank the members of the Microenvironment & Immunity Unit, the laboratory for Perception & Memory, the Stroma, Inflammation & Tissue Repair Unit, and the Biology and Genetics of the Bacterial Cell Wall Unit, for their support and feedback.
ANR-16-CE15-0021,PG-Brain,Modulation de l'activité du cerveau par le peptidoglycan bactérien(2016)
lepousez, gabriel
Modulation de l'activité du cerveau par le peptidoglycan bactérien - - PG-Brain2016 - ANR-16-CE15-0021 - AAPG2016 - VALID
Institut Pasteur [Paris] (IP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047)
Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Source :
Science, Science, 2022, 376 (6590), pp.eabj3986. ⟨10.1126/science.abj3986⟩
Publication Year :
2022
Publisher :
HAL CCSD, 2022.

Abstract

International audience; Gut bacteria influence brain functions and metabolism. We investigated whether this influence can be mediated by direct sensing of bacterial cell wall components by brain neurons. In mice, we found that bacterial peptidoglycan plays a major role in mediating gut-brain communication via the Nod2 receptor. Peptidoglycan-derived muropeptides reach the brain and alter the activity of a subset of brain neurons that express Nod2. Activation of Nod2 in hypothalamic inhibitory neurons is essential for proper appetite and body temperature control, primarily in females. This study identifies a microbe-sensing mechanism that regulates feeding behavior and host metabolism.

Subjects

Subjects :
Neurons
Mice
Multidisciplinary
Bacteria
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Nod2 Signaling Adaptor Protein
[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Animals
Appetite
Peptidoglycan
digestive system diseases
Body Temperature

Details

Language :
English
ISSN :
00368075 and 10959203
Database :
OpenAIRE
Journal :
Science, Science, 2022, 376 (6590), pp.eabj3986. ⟨10.1126/science.abj3986⟩
Accession number :
edsair.doi.dedup.....71cc3dc45b7a7f3d6038962410bedd17

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