Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner

Morgane Sonia Thion (1) , Donovan Low (2, 3) , Aymeric Silvin (2, 3) , Jinmiao Chen (2, 3) , Pauline Grisel (1) , Jonas Schulte-Schrepping (4) , Ronnie Blecher (5) , Thomas Ulas (4) , Paola Squarzoni (1) , Guillaume Hoeffel (6, 2, 3) , Fanny Coulpier (1, 7) , Eleni Siopi (8) , Friederike Sophie David (4) , Claus Scholz (4) , Foo Shihui (2, 3) , Josephine Lum (2, 3) , Arlaine Anne Amoyo (9) , Anis Larbi (2, 3) , Michael Poidinger (2, 3) , Anne Buttgereit (10) , Pierre-Marie Lledo (8) , Melanie Greter (10) , Jerry Kok Yen Chan (11) , Ido Amit (5) , Marc Beyer (4, 12) , Joachim Ludwig Schultze (4, 12) , Andreas Schlitzer (2, 3, 4) , Sven Pettersson (13, 14) , Florent Ginhoux (2, 3) , Sonia Garel (1)

1 IBENS - Institut de biologie de l'ENS Paris
2 SIgN - Singapore Immunology Network
3 A*STAR - Agency for science, technology and research [Singapore]
4 Universität Bonn = University of Bonn
5 Weizmann Institute of Science [Rehovot, Israël]
6 CIML - Centre d'Immunologie de Marseille - Luminy
7 Genomique ENS - GenomiqueENS
8 Perception et Mémoire / Perception and Memory
9 NCCS - National Cancer Centre Singapore
10 UZH - Universität Zürich [Zürich] = University of Zurich
11 KK Women's and Children's Hospital [Singapore]
12 DZNE - German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen
13 Nanyang Technological University [Singapour]
14 Karolinska Institutet [Stockholm]

Microglia are embryonically seeded macrophages that contribute to brain development, homeostasis, and pathologies. It is thus essential to decipher how microglial properties are temporally regulated by intrinsic and extrinsic factors, such as sexual identity and the microbiome. Here, we found that microglia undergo differentiation phases, discernable by transcriptomic signatures and chromatin accessibility landscapes, which can diverge in adult males and females. Remarkably, the absence of microbiome in germ-free mice had a time and sexually dimorphic impact both prenatally and postnatally: microglia were more profoundly perturbed in male embryos and female adults. Antibiotic treatment of adult mice triggered sexually biased microglial responses revealing both acute and long-term effects of microbiota depletion. Finally, human fetal microglia exhibited significant overlap with the murine transcriptomic signature. Our study shows that microglia respond to environmental challenges in a sex- and time-dependent manner from prenatal stages, with major implications for our understanding of microglial contributions to health and disease.

Mots clés: CXCR4; antibiotics; embryogenesis; germ-free; microbiome; microglia; neurodevelopmental disorders; neuroinflammation; prenatal; sex; CXCR4

Domaines: Immunologie

Morgane Sonia Thion, Donovan Low, Aymeric Silvin, Jinmiao Chen, Pauline Grisel, et al.. Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner. Cell, 2018, 172 (3), pp.500-516.e16. ⟨10.1016/j.cell.2017.11.042⟩. ⟨hal-02118049⟩