Host microbiota constantly control maturation and function of microglia in the central nervous system
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE67858 | GEO | 2015/05/25
SECONDARY ACCESSION(S): PRJNA281077
REPOSITORIES: GEO
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-05-25 | E-GEOD-67858 | biostudies-arrayexpress
Project description: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. For acute inflammatory challenges, LPS was applied intracranially and 6 hours later, animals were analyzed. Control animals were injected PBS i.c. Transcriptional profiles of FACS-sorted microglia were assessed using Affymetrix® (Santa Clara, USA) GeneChip Arrays (Mouse Gene 2.1 ST Arrays).
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Project description: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. 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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Project description: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.
2015-05-25 | GSE67857 | GEO
Project description: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.
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Project description: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.
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Project description: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.
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