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Intestinal Serum amyloid A suppresses systemic neutrophil activation and bactericidal activity in response to microbiota colonization.

Publication ,  Journal Article
Murdoch, CC; Espenschied, ST; Matty, MA; Mueller, O; Tobin, DM; Rawls, JF
Published in: PLoS Pathog
March 2019

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 depended 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.

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Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

March 2019

Volume

15

Issue

3

Start / End Page

e1007381

Location

United States

Related Subject Headings

  • Zebrafish
  • Virology
  • Signal Transduction
  • Serum Amyloid A Protein
  • Neutrophils
  • Neutrophil Activation
  • Microbiota
  • Liver
  • Intestines
  • Immunity, Innate
 

Citation

APA
Chicago
ICMJE
MLA
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Murdoch, C. C., Espenschied, S. T., Matty, M. A., Mueller, O., Tobin, D. M., & Rawls, J. F. (2019). Intestinal Serum amyloid A suppresses systemic neutrophil activation and bactericidal activity in response to microbiota colonization. PLoS Pathog, 15(3), e1007381. https://doi.org/10.1371/journal.ppat.1007381
Murdoch, Caitlin C., Scott T. Espenschied, Molly A. Matty, Olaf Mueller, David M. Tobin, and John F. Rawls. “Intestinal Serum amyloid A suppresses systemic neutrophil activation and bactericidal activity in response to microbiota colonization.PLoS Pathog 15, no. 3 (March 2019): e1007381. https://doi.org/10.1371/journal.ppat.1007381.
Murdoch CC, Espenschied ST, Matty MA, Mueller O, Tobin DM, Rawls JF. Intestinal Serum amyloid A suppresses systemic neutrophil activation and bactericidal activity in response to microbiota colonization. PLoS Pathog. 2019 Mar;15(3):e1007381.
Murdoch, Caitlin C., et al. “Intestinal Serum amyloid A suppresses systemic neutrophil activation and bactericidal activity in response to microbiota colonization.PLoS Pathog, vol. 15, no. 3, Mar. 2019, p. e1007381. Pubmed, doi:10.1371/journal.ppat.1007381.
Murdoch CC, Espenschied ST, Matty MA, Mueller O, Tobin DM, Rawls JF. Intestinal Serum amyloid A suppresses systemic neutrophil activation and bactericidal activity in response to microbiota colonization. PLoS Pathog. 2019 Mar;15(3):e1007381.

Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

March 2019

Volume

15

Issue

3

Start / End Page

e1007381

Location

United States

Related Subject Headings

  • Zebrafish
  • Virology
  • Signal Transduction
  • Serum Amyloid A Protein
  • Neutrophils
  • Neutrophil Activation
  • Microbiota
  • Liver
  • Intestines
  • Immunity, Innate