10.5061/DRYAD.174667C
Murdoch, Caitlin
Duke University
Espenschied, Scott
Duke University
Matty, Molly
Duke University
Mueller, Olaf
Duke University
Tobin, David
Duke University
Rawls, John
Duke University
Data from: Intestinal Serum Amyloid A suppresses systemic neutrophil
activation and bactericidal activity in response to microbiota
colonization
Dryad
dataset
2019
serum amyloid A
Danio rerio
neutrophil
2019-03-13T21:21:04Z
2019-03-13T21:21:04Z
en
https://doi.org/10.1371/journal.ppat.1007381
9950625246 bytes
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CC0 1.0 Universal (CC0 1.0) Public Domain Dedication
The intestinal microbiota influences the development and function of
myeloid lineages such as neutrophils, but the underlying molecular
mechanisms are unresolved. Using gnotobiotic zebrafish, we identified the
immune effector Serum amyloid A (Saa) as one of the most highly induced
transcripts in digestive tissues following microbiota colonization. Saa is
a conserved secreted protein produced in the intestine and liver with
described effects on neutrophils in vitro, however its in vivo functions
remain poorly defined. We engineered saa mutant zebrafish to test
requirements for Saa on innate immunity in vivo. Zebrafish mutant for saa
displayed impaired neutrophil responses to wounding but augmented
clearance of pathogenic bacteria. At baseline, saa mutants exhibited
moderate neutrophilia and altered neutrophil tissue distribution.
Molecular and functional analyses of isolated neutrophils revealed that
Saa suppresses expression of pro-inflammatory markers and bactericidal
activity. Saa’s effects on neutrophils depend on microbiota colonization,
suggesting this protein mediates the microbiota’s effects on host innate
immunity. To test tissue-specific roles of Saa on neutrophil function, we
over-expressed saa in the intestine or liver and found that sufficient to
partially complement neutrophil phenotypes observed in saa mutants. These
results indicate Saa produced by the intestine in response to microbiota
serves as a systemic signal to neutrophils to restrict aberrant
activation, decreasing inflammatory tone and bacterial killing potential
while simultaneously enhancing their ability to migrate to wounds.
Fig1These file archives contain the raw data used in
PPATHOGENS-D-18-01928R1. It includes excel files (.xlsx), image files
(.lif, .tif, .czi), and text files (.txt). For complete details regarding
generation of data presented in this paper please see the corresponding
materials and methods sectionFig2Fig3Fig4Fig5S1 FigS2 FigS3 FigS4 FigS5
FigS6 FigS7 FigS8 Fig