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

Michelle Kanther, Sarah Tomkovich, Sun Xiaolun, Melinda R. Grosser, Ja Seol Koo, Edward J. Flynn, Christian Jobin, John F. Rawls

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Summary: 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.

Original languageEnglish
Pages (from-to)1053-1067
Number of pages15
JournalCellular Microbiology
Volume16
Issue number7
DOIs
Publication statusPublished - 2014 Jan 1
Externally publishedYes

Fingerprint

Serum Amyloid A Protein
Microbiota
Neutrophils
Zebrafish
Germ-Free Life
Neutrophil Infiltration
Acute-Phase Proteins
Wounds and Injuries
Peroxidase
Intestines
Leukocytes
Homeostasis

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology
  • Medicine(all)

Cite this

Kanther, M., Tomkovich, S., Xiaolun, S., Grosser, M. R., Koo, J. S., Flynn, E. J., ... Rawls, J. F. (2014). Commensal microbiota stimulate systemic neutrophil migration through induction of Serum amyloid A. Cellular Microbiology, 16(7), 1053-1067. https://doi.org/10.1111/cmi.12257

Commensal microbiota stimulate systemic neutrophil migration through induction of Serum amyloid A. / Kanther, Michelle; Tomkovich, Sarah; Xiaolun, Sun; Grosser, Melinda R.; Koo, Ja Seol; Flynn, Edward J.; Jobin, Christian; Rawls, John F.

In: Cellular Microbiology, Vol. 16, No. 7, 01.01.2014, p. 1053-1067.

Research output: Contribution to journalArticle

Kanther, M, Tomkovich, S, Xiaolun, S, Grosser, MR, Koo, JS, Flynn, EJ, Jobin, C & Rawls, JF 2014, 'Commensal microbiota stimulate systemic neutrophil migration through induction of Serum amyloid A', Cellular Microbiology, vol. 16, no. 7, pp. 1053-1067. https://doi.org/10.1111/cmi.12257
Kanther, Michelle ; Tomkovich, Sarah ; Xiaolun, Sun ; Grosser, Melinda R. ; Koo, Ja Seol ; Flynn, Edward J. ; Jobin, Christian ; Rawls, John F. / Commensal microbiota stimulate systemic neutrophil migration through induction of Serum amyloid A. In: Cellular Microbiology. 2014 ; Vol. 16, No. 7. pp. 1053-1067.
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