Microglial control of astrocytes in response to microbial metabolites

Rothhammer V, Borucki DM, Tjon EC, Takenaka MC, Chao CC, Ardura-Fabregat A, De Lima KA, Gutierrez-Vazquez C, Hewson P, Staszewski O, Blain M, Healy L, Neziraj T, Borio M, Wheeler M, Dragin LL, Laplaud DA, Antel J, Alvarez JI, Prinz M, Quintana FJ (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Nature Nature Research

Book Volume: 557

Pages Range: 724-728

Journal Issue: 7707

DOI: 10.1038/s41586-018-0119-x

Abstract

Microglia and astrocytes modulate inflammation and neurodegeneration in the central nervous system (CNS) 1-3 . Microglia modulate pro-inflammatory and neurotoxic activities in astrocytes, but the mechanisms involved are not completely understood 4,5 . Here we report that TGFα and VEGF-B produced by microglia regulate the pathogenic activities of astrocytes in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Microglia-derived TGFα acts via the ErbB1 receptor in astrocytes to limit their pathogenic activities and EAE development. Conversely, microglial VEGF-B triggers FLT-1 signalling in astrocytes and worsens EAE. VEGF-B and TGFα also participate in the microglial control of human astrocytes. Furthermore, expression of TGFα and VEGF-B in CD14+ cells correlates with the multiple sclerosis lesion stage. Finally, metabolites of dietary tryptophan produced by the commensal flora control microglial activation and TGFα and VEGF-B production, modulating the transcriptional program of astrocytes and CNS inflammation through a mechanism mediated by the aryl hydrocarbon receptor. In summary, we identified positive and negative regulators that mediate the microglial control of astrocytes. Moreover, these findings define a pathway through which microbial metabolites limit pathogenic activities of microglia and astrocytes, and suppress CNS inflammation. This pathway may guide new therapies for multiple sclerosis and other neurological disorders.

Authors with CRIS profile

Veit Rothhammer

Involved external institutions

Harvard University US United States (USA) (US) National Institute for Health and Medical Research / Institut national de la santé et de la recherche médicale (INSERM) FR France (FR) Albert-Ludwigs-Universität Freiburg DE Germany (DE) University of Pennsylvania US United States (USA) (US) McGill University CA Canada (CA)

How to cite

APA:

Rothhammer, V., Borucki, D.M., Tjon, E.C., Takenaka, M.C., Chao, C.-C., Ardura-Fabregat, A.,... Quintana, F.J. (2018). Microglial control of astrocytes in response to microbial metabolites. Nature, 557(7707), 724-728. https://doi.org/10.1038/s41586-018-0119-x

MLA:

Rothhammer, Veit, et al. "Microglial control of astrocytes in response to microbial metabolites." Nature 557.7707 (2018): 724-728.

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