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

Stacey L. Burgess, Mahmoud Saleh, Carrie A. Cowardin, Erica Buonomo, Zannatun Noor, Koji Watanabe, Mayuresh Abhyankar, Stephane Lajoie, Marsha Wills-Karp, William A. Petri

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)2824-2832
Number of pages9
JournalInfection and immunity
Volume84
Issue number10
DOIs
StatePublished - 2016

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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