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Sensing of the microbiota by NOD1 in mesenchymal stromal cells regulates murine hematopoiesis.
Iwamura, Chiaki; Bouladoux, Nicolas; Belkaid, Yasmine; Sher, Alan; Jankovic, Dragana.
Afiliação
  • Iwamura C; Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases.
  • Bouladoux N; NIAID Microbiome Program, and.
  • Belkaid Y; Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
  • Sher A; NIAID Microbiome Program, and.
  • Jankovic D; Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Blood ; 129(2): 171-176, 2017 01 12.
Article em En | MEDLINE | ID: mdl-27799160
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteína Adaptadora de Sinalização NOD1 / Células-Tronco Mesenquimais / Microbiota / Hematopoese Limite: Animals Idioma: En Revista: Blood Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteína Adaptadora de Sinalização NOD1 / Células-Tronco Mesenquimais / Microbiota / Hematopoese Limite: Animals Idioma: En Revista: Blood Ano de publicação: 2017 Tipo de documento: Article