Sensing of the microbiota by NOD1 in mesenchymal stromal cells regulates murine hematopoiesis

Blood. 2017 Jan 12;129(2):171-176. doi: 10.1182/blood-2016-06-723742. Epub 2016 Oct 31.

Abstract

The microbiota is known to influence the generation of hematopoietic progenitors, although the pathways underlying this process are still poorly understood. NOD1 and NOD2 are intracellular sensors for both Gram-positive and Gram-negative bacteria, but their role in steady-state hematopoiesis has never been characterized. We observed that stimulation with NOD1 or NOD2 ligand had no effect on the survival/proliferation of hematopoietic precursors. Nonetheless, NOD1, but not NOD2, ligand induced expression of multiple hematopoietic cytokines (interleukin-7 [IL-7], Flt3L, stem cell factor [SCF], ThPO, and IL-6) from bone marrow mesenchymal stromal cells (MSCs) in vitro. Moreover, in vivo administration of NOD1 ligand to germ-free mice restored the numbers of hematopoietic stem cells and precursors in bone marrow as well as serum concentrations of IL-7, Flt3L, SCF, and ThPO to the levels displayed by specific pathogen-free control animals. Based on these findings, we propose that NOD1 signaling in MSCs serves as an important pathway underlying the requirement for microbiota in the maintenance of steady-state hematopoiesis. This function is distinct from that triggered by lipopolysaccharide in both its broad effects on multiple progenitors and specific targeting of MSCs as cytokine producing intermediates.

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism
  • Cell Separation
  • Cells, Cultured
  • Flow Cytometry
  • Germ-Free Life
  • Hematopoiesis / physiology*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microbiota*
  • Nod1 Signaling Adaptor Protein / metabolism*
  • Polymerase Chain Reaction

Substances

  • Nod1 Signaling Adaptor Protein
  • Nod1 protein, mouse