PUBLICATION

Critical Role for a Subset of Intestinal Macrophages in Shaping Gut Microbiota in Adult Zebrafish

Authors
Earley, A.M., Graves, C.L., Shiau, C.E.
ID
ZDB-PUB-181012-9
Date
2018
Source
Cell Reports   25: 424-436 (Journal)
Registered Authors
Shiau, Celia
Keywords
c1q, complement, interferon regulatory factor, intestinal macrophages, irf8, microbiota, microglia, zebrafish
Datasets
GEO:GSE159845
MeSH Terms
  • Macrophages/immunology
  • Macrophages/metabolism
  • Macrophages/microbiology*
  • Animals, Genetically Modified
  • Interferon Regulatory Factors/genetics
  • Interferon Regulatory Factors/metabolism*
  • Gastrointestinal Microbiome*
  • Brain/immunology
  • Brain/metabolism
  • Brain/microbiology*
  • Complement C1q/metabolism*
  • Cells, Cultured
  • Mutation*
  • Zebrafish
  • Animals
(all 15)
PubMed
30304682 Full text @ Cell Rep.
Abstract
The gut microbiota is strongly influenced by environmental factors, although host contribution is far less understood. We leveraged macrophage-deficient interferon regulatory factor irf8 zebrafish mutants to investigate the role of macrophages in this process. In conventionally raised adult irf8-deficient mutants, we found a significant loss of intestinal macrophages associated with a strikingly altered gut microbiota when compared to co-housed siblings. The destabilization of the gut commensal microbiota was associated with a severe reduction in complement C1q genes and outgrowth of a rare bacterial species. Consistent with a critical function of irf8 in adult intestinal macrophages, irf8 is abundantly expressed in these cells normally, and restoring macrophage irf8 expression in irf8 mutants was sufficient to recover commensal microbes and C1q genes expression. This study reports an important subpopulation of intestinal macrophages that requires irf8 to establish in the gut, ensure normal colonization of gut microbes, and prevent immune dysregulation.
Genes / Markers
Figures
Figure Gallery (7 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
gl22TgTransgenic Insertion
    nz50TgTransgenic Insertion
      st95
        Small Deletion
        zf149TgTransgenic Insertion
          1 - 4 of 4
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          Human Disease / Model
          No data available
          Sequence Targeting Reagents
          No data available
          Fish
          No data available
          Antibodies
          No data available
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          DsRed2EFGDsRed2
          EGFPEFGEGFP
          GAL4EFGGAL4
          1 - 3 of 3
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          Mapping
          No data available