Host microbiota constantly control maturation and function of microglia in the CNS
| Autor: | Eunyoung Chun, Hadas Keren-Shaul, Diego Jaitin, Eyal David, Vera Schwierzeck, Kathy D. McCoy, Wendy S. Garrett, Olaf Utermöhlen, Peter Staeheli, Tanel Mahlakõiv, Daniel Erny, Ido Amit, Anna Lena Hrabě de Angelis, Thorsten Buch, Andreas Diefenbach, Ori Staszewski, Peter Wieghofer, Marco Prinz, Bärbel Stecher, Kristin Jakobshagen |
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| Přispěvatelé: | University of Zurich, Prinz, Marco |
| Rok vydání: | 2014 |
| Předmět: |
Central Nervous System
Male Cell Gut–brain axis 610 Medicine & health Biology digestive system Receptors G-Protein-Coupled Mice Immunity medicine Animals Homeostasis 10239 Institute of Laboratory Animal Science Receptor Innate immune system Microglia General Neuroscience Microbiota 2800 General Neuroscience Fatty Acids Volatile Phenotype Immunity Innate Mice Inbred C57BL medicine.anatomical_structure nervous system Immunology 570 Life sciences biology 590 Animals (Zoology) Female Neuroscience |
| Zdroj: | Nature neuroscience. 18(7) |
| ISSN: | 1546-1726 |
| Popis: | As the tissue macrophages of the CNS, microglia are critically involved in diseases of the CNS. However, it remains unknown what controls their maturation and activation under homeostatic conditions. We observed substantial contributions of the host microbiota to microglia homeostasis, as germ-free (GF) mice displayed global defects in microglia with altered cell proportions and an immature phenotype, leading to impaired innate immune responses. Temporal eradication of host microbiota severely changed microglia properties. Limited microbiota complexity also resulted in defective microglia. In contrast, recolonization with a complex microbiota partially restored microglia features. We determined that short-chain fatty acids (SCFA), microbiota-derived bacterial fermentation products, regulated microglia homeostasis. Accordingly, mice deficient for the SCFA receptor FFAR2 mirrored microglia defects found under GF conditions. These findings suggest that host bacteria vitally regulate microglia maturation and function, whereas microglia impairment can be rectified to some extent by complex microbiota. |
| Databáze: | OpenAIRE |
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