Host microbiota constantly control maturation and function of microglia in the CNS
Daniel Erny,Anna Lena Hrabě de Angelis,Diego Jaitin,Peter Wieghofer,Ori Staszewski,Eyal David,Hadas Keren-Shaul,Tanel Mahlakõiv,Kristin Jakobshagen,Thorsten Buch,Vera Schwierzeck,Olaf Utermöhlen,Eunyoung Chun,Wendy S. Garrett,Kathy D. McCoy,Andreas Diefenbach,Peter Staeheli,Bärbel Stecher,Ido Amit,Marco Prinz +19 more
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TLDR
It is determined that short-chain fatty acids (SCFA), microbiota-derived bacterial fermentation products, regulated microglia homeostasis and mice deficient for the SCFA receptor FFAR2 mirroredmicroglia defects found under GF conditions, suggesting that host bacteria vitally regulate microglian maturation and function.Abstract:
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.read more
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Communicating systems in the body: how microbiota and microglia cooperate
TL;DR: New aspects of the interaction between host microbiota and brain function with special focus on the brain‐resident innate immune cells, the microglia are discussed.
Journal ArticleDOI
Do bacteria shape our development? Crosstalk between intestinal microbiota and HPA axis.
TL;DR: Current knowledge on the developmental crosstalk between the intestinal microbiota and the HPA axis is summarized, providing a basis for understanding the development and bidirectional communication between these two essential systems in human functioning.
Journal ArticleDOI
Environmental Control of Astrocyte Pathogenic Activities in CNS Inflammation.
Michael A. Wheeler,Merja Jaronen,Ruxandra Covacu,Stephanie Zandee,Giulia Scalisi,Veit Rothhammer,Emily C. Tjon,Chun-Cheih Chao,Jessica E. Kenison,Manon Blain,Vijayaraghava T.S. Rao,Patrick Hewson,Andreia Barroso,Cristina Gutiérrez-Vázquez,Alexandre Prat,Jack P. Antel,Russ Hauser,Francisco J. Quintana,Francisco J. Quintana +18 more
TL;DR: These studies define environmental mechanisms that control astrocyte pathogenic activities and establish a multidisciplinary approach for the systematic investigation of the effects of environmental exposure in neurologic disorders.
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Gut-licensed IFNγ+ NK cells drive LAMP1+TRAIL+ anti-inflammatory astrocytes
Liliana Maria Sanmarco,Michael A. Wheeler,Michael A. Wheeler,Cristina Gutiérrez-Vázquez,Carolina Manganeli Polonio,Mathias Linnerbauer,Felipe A. Pinho-Ribeiro,Zhaorong Li,Zhaorong Li,Federico Giovannoni,Katelyn V. Batterman,Giulia Scalisi,Stephanie Zandee,Evelyn S. Heck,Moneera Alsuwailm,Moneera Alsuwailm,Douglas L. Rosene,Burkhard Becher,Isaac M. Chiu,Alexandre Prat,Francisco J. Quintana,Francisco J. Quintana +21 more
TL;DR: In this article, the authors identify a subset of astrocytes that express the lysosomal protein LAMP12 and the death receptor ligand TRAIL3 and show that LAMP1+TRAIL+astrocyte limit inflammation in the central nervous system by inducing T cell apoptosis through TRAIL-DR5 signalling.
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Harnessing Gut Microbes for Mental Health: Getting From Here to There.
TL;DR: Current understanding of gut microbial influence over physiological function is summarized, with an emphasis on neurobehavioral and neurological impairment based on growing understanding of the gut-brain axis.
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