PUBLICATION

Commensal microbiota stimulate systemic neutrophil migration through induction of Serum amyloid A

Authors
Kanther, M., Tomkovich, S., Xiaolun, S., Grosser, M.R., Koo, J., Flynn, E.J., Jobin, C., and Rawls, J.F.
ID
ZDB-PUB-140224-43
Date
2014
Source
Cellular Microbiology   16(7): 1053-67 (Journal)
Registered Authors
Flynn, Edward J., Kanther, Michelle, Rawls, John F.
Keywords
none
MeSH Terms
  • Animals
  • Biomarkers/metabolism
  • Cell Line
  • Chemotaxis, Leukocyte*
  • Gene Expression
  • Immunity, Innate
  • Inflammation Mediators/metabolism
  • Mice, Inbred C57BL
  • Microbiota/immunology*
  • NF-kappa B/metabolism
  • Neutrophils/immunology*
  • Organ Specificity
  • Serum Amyloid A Protein/genetics
  • Serum Amyloid A Protein/metabolism*
  • Signal Transduction
  • Transcriptional Activation
  • Wound Healing/immunology
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
24373309 Full text @ Cell. Microbiol.
Abstract

Neutrophils serve critical roles in inflammatory responses to infection and injury, and mechanisms governing their activity represent attractive targets for controlling inflammation. The commensal microbiota is known to regulate the activity of neutrophils and other leucocytes in the intestine, but the systemic impact of the microbiota on neutrophils remains unknown. Here we utilized in vivo imaging in gnotobiotic zebrafish to reveal diverse effects of microbiota colonization on systemic neutrophil development and function. The presence of a microbiota resulted in increased neutrophil number and myeloperoxidase expression, and altered neutrophil localization and migratory behaviours. These effects of the microbiota on neutrophil homeostasis were accompanied by an increased recruitment of neutrophils to injury. Genetic analysis identified the microbiota-induced acute phase protein serum amyloid A (Saa) as a host factor mediating microbial stimulation of tissue-specific neutrophil migratory behaviours. In vitro studies revealed that zebrafish cells respond to Saa exposure by activating NF-κB, and that Saa-dependent neutrophil migration requires NF-κB-dependent gene expression. These results implicate the commensal microbiota as an important environmental factor regulating diverse aspects of systemic neutrophil development and function, and reveal a critical role for a Saa-NF-κB signalling axis in mediating neutrophil migratory responses.

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Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
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Mapping