Details

Autor(en) / Beteiligte

• Yan, Hannah
• Walker, Forrest C.
• Ali, Arushana
• Han, Hyojeong
• Tan, Lin
• Veillon, Lucas
• Lorenzi, Philip L.
• Baldridge, Megan T.
• King, Katherine Y.

Titel

The bacterial microbiota regulates normal hematopoiesis via metabolite-induced type 1 interferon signaling

Ist Teil von

• Blood advances, 2022-03, Vol.6 (6), p.1754-1765

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2022

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Antibiotic therapy, especially when administered long term, is associated with adverse hematologic effects such as cytopenia. Signals from the intestinal microbiota are critical to maintain normal hematopoiesis, and antibiotics can cause bone marrow suppression through depletion of the microbiota. We reported previously that STAT1 signaling is necessary for microbiota-dependent hematopoiesis, but the precise mechanisms by which the gut microbiota signals to the host bone marrow to regulate hematopoiesis remain undefined. We sought to identify the cell type(s) through which STAT1 promotes microbiota-mediated hematopoiesis and to elucidate which upstream signaling pathways trigger STAT1 signaling. Using conditional knockout and chimeric mice, we found that the microbiota induced STAT1 signaling in non-myeloid hematopoietic cells to support hematopoiesis and that STAT1 signaling was specifically dependent on type I interferons (IFNs). Indeed, basal type I IFN signaling was reduced in hematopoietic progenitor cells with antibiotic treatment. In addition, we discovered that oral administration of a commensal-derived product, NOD1 ligand, rescues the hematopoietic defects induced by antibiotics in mice. Using metabolomics, we identified additional microbially produced candidates that can stimulate type I IFN signaling to potentially rescue the hematopoietic defects induced by antibiotics, including phosphatidylcholine and γ-glutamylalanine. Overall, our studies define a signaling pathway through which microbiota promotes normal hematopoiesis and identify microbial metabolites that may serve as therapeutic agents to ameliorate antibiotic-induced bone marrow suppression and cytopenia. •The intestinal microbiota promotes hematopoiesis by activating type I IFN and STAT1 signaling.•Metabolites of the intestinal microbiota such as NOD1 ligand can rescue hematopoiesis in antibiotic-treated mice. [Display omitted]