title: Sensing of the microbiota by NOD1 in mesenchymal stromal cells regulates murine hematopoiesis.
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.
authors: Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases.
authors: Chiaki
authors: C
authors: Iwamura
authors: NIAID Microbiome Program, and.|Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
authors: Nicolas
authors: N
authors: Bouladoux
authors: NIAID Microbiome Program, and.|Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
authors: Yasmine
authors: Y
authors: Belkaid
authors: Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases.
authors: Alan
authors: A
authors: Sher
authors: Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases.
authors: Dragana
authors: 0000-0001-7360-1809
authors: D
authors: Jankovic
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D005434:Flow Cytometry; D005856:Germ-Free Life; D006410:Hematopoiesis / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064307:Microbiota; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism*; D016133:Polymerase Chain Reaction
chemical_list: D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse