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

• DOI: 10.1128/iai.00316-16
• Publication Date: 2016-07-26T02:28:50Z
• Authors: Stacey L. Burgess; Mahmoud Saleh; Carrie A. Cowardin; Erica Buonomo; Zannatun Noor; Koji Watanabe; Mayuresh Abhyankar; Stephane Lajoie; Marsha Wills-Karp; William A. Petri
• Keywords: Male; 0301 basic medicine; Jumonji Domain-Containing Histone Demethylases; Serum Amyloid A Protein; Bacteria; Entamoebiasis; Entamoeba histolytica; Granulocyte-Macrophage Colony-Stimulating Factor; Bone Marrow Cells; Dendritic Cells; 3. Good health; Gastrointestinal Tract; Mice, Inbred C57BL; Disease Models, Animal; Mice; 03 medical and health sciences; Bone Marrow; Granulocyte-Macrophage Progenitor Cells; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; Animals

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.