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

  • Thion MS Institut de Biologie de l'Ecole normale supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Research University, 75005 Paris, France.
  • Low D Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore.
  • Silvin A Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore.
  • Chen J Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore.
  • Grisel P Institut de Biologie de l'Ecole normale supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Research University, 75005 Paris, France.
  • Schulte-Schrepping J Genomics and Immunoregulation, Life and Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany.
  • Blecher R Department of Immunology, Weizmann Institute of Science, 76100 Rehovot, Israel.
  • Ulas T Genomics and Immunoregulation, Life and Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany.
  • Squarzoni P Institut de Biologie de l'Ecole normale supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Research University, 75005 Paris, France.
  • Hoeffel G Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore; Aix-Marseille Université, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy (CIML), 13288 Marseille, France.
  • Coulpier F Institut de Biologie de l'Ecole normale supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Research University, 75005 Paris, France.
  • Siopi E Institut Pasteur, Unité Perception et Mémoire, CNRS, UMR 3571, F-75015 Paris, France.
  • David FS Genomics and Immunoregulation, Life and Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany.
  • Scholz C Genomics and Immunoregulation, Life and Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany.
  • Shihui F Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore.
  • Lum J Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore.
  • Amoyo AA National Cancer Centre, Singapore 169610, Singapore.
  • Larbi A Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore.
  • Poidinger M Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore.
  • Buttgereit A Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland.
  • Lledo PM Institut Pasteur, Unité Perception et Mémoire, CNRS, UMR 3571, F-75015 Paris, France.
  • Greter M Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland.
  • Chan JKY Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore 229899, Singapore; KK Research Centre, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore.
  • Amit I Department of Immunology, Weizmann Institute of Science, 76100 Rehovot, Israel.
  • Beyer M Genomics and Immunoregulation, Life and Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany; Molecular Immunology in Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany.
  • Schultze JL Genomics and Immunoregulation, Life and Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany; Platform of Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, 53175 Bonn, Germany.
  • Schlitzer A Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore; Myeloid Cell Biology, LIMES-Institute, University of Bonn, 53115 Bonn, Germany.
  • Pettersson S Lee Kong Chian School of Medicine and School of Biological Sciences, Nanyang Technological University, Singapore 639798, Singapore; Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm 17165, Sweden.
  • Ginhoux F Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore. Electronic address: florent_ginhoux@immunol.a-star.edu.sg.
  • Garel S Institut de Biologie de l'Ecole normale supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Research University, 75005 Paris, France. Electronic address: garel@biologie.ens.fr.
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  • 2017-12-26
Published in:
  • Cell. - 2018
CXCR4
antibiotics
embryogenesis
germ-free
microbiome
microglia
neurodevelopmental disorders
neuroinflammation
prenatal
sex
Animals
Brain
Cell Differentiation
Cells, Cultured
Chromatin Assembly and Disassembly
Female
Germ-Free Life
Humans
Male
Mice
Mice, Inbred C57BL
Microbiota
Microglia
Pregnancy
Prenatal Exposure Delayed Effects
Sex Factors
Transcriptome
English 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.
Language
  • English
Open access status
hybrid
Identifiers
Persistent URL
https://folia.unifr.ch/global/documents/91189
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