title: Commensal microbiota stimulate systemic neutrophil migration through induction of serum amyloid A.
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.
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Kanther
authors.forename: Sarah
authors.initials: S
authors.lastname: Tomkovich
authors.forename: Sun
authors.initials: S
authors.lastname: Xiaolun
authors.forename: Melinda R
authors.initials: MR
authors.lastname: Grosser
authors.forename: Jaseol
authors.initials: J
authors.lastname: Koo
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Flynn
authors.forename: Christian
authors.initials: C
authors.lastname: Jobin
authors.forename: John F
authors.initials: JF
authors.lastname: Rawls
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D002634:Chemotaxis, Leukocyte; D015870:Gene Expression; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology*; D009928:Organ Specificity; D000685:Serum Amyloid A Protein / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation; D014945:Wound Healing / Q000276:immunology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D016328:NF-kappa B; D000685:Serum Amyloid A Protein; D029961:Zebrafish Proteins