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| Status |
Public on May 25, 2015 |
| Title |
Host microbiota constantly control maturation and function of microglia in the central nervous system (part 2) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
As tissue macrophages of the central nervous system (CNS), microglia are critically involved in diseases of the CNS. However, it remains unknown what controls their maturation and activation under homeostatic conditions. Here we reveal significant 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, regulate microglia homeostasis. Accordingly, mice deficient for the SCFA receptor FFAR2 mirrored microglia defects found under GF conditions. These findings reveal that host bacteria vitally regulate microglia maturation and function, whereas microglia impairment can be restored to some extent by complex microbiota.
We used microarrays to determine the gene expression of microglia after LCMV challenge.
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| Overall design |
Lymphocytic Choriomeningitis Virus (LCMV) strain WE was propagated and titrated as plaque forming units (PFU) on L929 cells as described before (Herz,J. et al. Acid sphingomyelinase is a key regulator of cytotoxic granule secretion by primary T lymphocytes. Nat. Immunol. 10, 761-768 (2009)). PFU were multiplied by the factor 10 to be converted into infectious units (IU). Mice were infected by intracerebral inoculation of 103 IU into the right hemisphere.
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| Contributor(s) |
Erny D, Hrabě de Angelis AL, Jaitin D, Wieghofer P, Staszewski O, David E, Keren-Shaul H, Mahlakoiv T, Jakobshagen K, Buch T, Schwierzeck V, Utermöhlen O, Chun E, Garrett WS, McCoy KD, Diefenbach A, Staeheli P, Stecher B, Amit I, Prinz M |
| Citation(s) |
26030851 |
| Submission date |
Apr 14, 2015 |
| Last update date |
Mar 08, 2018 |
| Contact name |
Ori Staszewski |
| E-mail(s) |
ori.staszewski@uniklinik-freiburg.de
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| Organization name |
University Medical Center Freiburg
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| Department |
Institute of Neuropathology
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| Street address |
Breisacher Str. 64
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| City |
Freiburg |
| ZIP/Postal code |
D-79106 |
| Country |
Germany |
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| Platforms (1) |
| GPL17400 |
[MoGene-2_1-st] Affymetrix Mouse Gene 2.1 ST Array [transcript (gene) version] |
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| Samples (20)
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| GSM1657294 |
Microglia_specificpathogenfree_4d_after_LCMV_ic_01 |
| GSM1657295 |
Microglia_specificpathogenfree_4d_after_LCMV_ic_02 |
| GSM1657296 |
Microglia_specificpathogenfree_4d_after_LCMV_ic_03 |
| GSM1657297 |
Microglia_specificpathogenfree_4d_after_LCMV_ic_04 |
| GSM1657298 |
Microglia_specificpathogenfree_4d_after_LCMV_ic_05 |
| GSM1657299 |
Microglia_specificpathogenfree_4d_after_LCMV_ic_06 |
| GSM1657300 |
Microglia_specificpathogenfree_4d_after_LCMV_ic_07 |
| GSM1657301 |
Microglia_specificpathogenfree_4d_after_LCMV_ic_08 |
| GSM1657302 |
Microglia_specificpathogenfree_4d_after_LCMV_ic_09 |
| GSM1657303 |
Microglia_specificpathogenfree_4d_after_LCMV_ic_10 |
| GSM1657304 |
Microglia_germfree_4d_after_LCMV_ic_01 |
| GSM1657305 |
Microglia_germfree_4d_after_LCMV_ic_02 |
| GSM1657306 |
Microglia_germfree_4d_after_LCMV_ic_03 |
| GSM1657307 |
Microglia_germfree_4d_after_LCMV_ic_04 |
| GSM1657308 |
Microglia_germfree_4d_after_LCMV_ic_05 |
| GSM1657309 |
Microglia_germfree_4d_after_LCMV_ic_06 |
| GSM1657310 |
Microglia_germfree_4d_after_LCMV_ic_07 |
| GSM1657311 |
Microglia_germfree_4d_after_LCMV_ic_08 |
| GSM1657312 |
Microglia_germfree_4d_after_LCMV_ic_09 |
| GSM1657313 |
Microglia_germfree_4d_after_LCMV_ic_10 |
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| This SubSeries is part of SuperSeries: |
| GSE67858 |
Host microbiota constantly control maturation and function of microglia in the central nervous system |
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| Relations |
| BioProject |
PRJNA281079 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE67857_RAW.tar |
98.7 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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