title: Role of Serum Amyloid A, Granulocyte-Macrophage Colony-Stimulating Factor, and Bone Marrow Granulocyte-Monocyte Precursor Expansion in Segmented Filamentous Bacterium-Mediated Protection from Entamoeba histolytica.
abstract: Intestinal segmented filamentous bacteria (SFB) protect from ameba infection, and protection is transferable with bone marrow dendritic cells (BMDCs). SFB cause an increase in serum amyloid A (SAA), suggesting that SAA might mediate SFB's effects on BMDCs. Here we further explored the role of bone marrow in SFB-mediated protection. Transient gut colonization with SFB or SAA administration alone transiently increased the H3K27 histone demethylase Jmjd3, persistently increased bone marrow Csf2ra expression and granulocyte monocyte precursors (GMPs), and protected from ameba infection. Pharmacologic inhibition of Jmjd3 H3K27 demethylase activity during SAA treatment or blockade of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling in SFB-colonized mice prevented GMP expansion, decreased gut neutrophils, and blocked protection from ameba infection. These results indicate that alteration of the microbiota and systemic exposure to SAA can influence myelopoiesis and susceptibility to amebiasis via epigenetic mechanisms. Gut microbiota-marrow communication is a previously unrecognized mechanism of innate protection from infection.
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Burgess
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Saleh
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Cowardin
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Erica
authors.initials: E
authors.lastname: Buonomo
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Zannatun
authors.initials: Z
authors.lastname: Noor
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Mayuresh
authors.initials: M
authors.lastname: Abhyankar
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Stephane
authors.initials: S
authors.lastname: Lajoie
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Marsha
authors.initials: M
authors.lastname: Wills-Karp
authors.affiliation: Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia, USA wap3g@virginia.edu.
authors.forename: William A
authors.initials: WA
authors.lastname: Petri
mesh_terms: D000818:Animals; D001419:Bacteria; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000502:physiology; D003713:Dendritic Cells / Q000378:metabolism; D004195:Disease Models, Animal; D004748:Entamoeba histolytica / Q000502:physiology*; D004749:Entamoebiasis / Q000503:physiopathology*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology*; D055014:Granulocyte-Macrophage Progenitor Cells; D056484:Jumonji Domain-Containing Histone Demethylases / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000502:physiology*
chemical_list: D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D000685:Serum Amyloid A Protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D056484:Jumonji Domain-Containing Histone Demethylases