Abstract
Inflammation alters hematopoiesis, often by decreasing erythropoiesis and enhancing myeloid output. The mechanisms behind these changes and how the BM stroma contributes to this process are active areas of research. In this study, we examine these questions in the setting of murine Toxoplasma gondii infection. Our data reveal that infection alters early myeloerythroid differentiation, blocking erythroid development beyond the Pre MegE stage, while expanding the GMP population. IL-6 was found to be a critical mediator of these differences, independent of hepcidin-induced iron restriction. Comparing the BM with the spleen showed that the hematopoietic response was driven by the local microenvironment, and BM chimeras demonstrated that radioresistant cells were the relevant source of IL-6 in vivo. Finally, direct ex vivo sorting revealed that VCAM(+)CD146(lo) BM stromal fibroblasts significantly increase IL-6 secretion after infection. These data suggest that BMSCs regulate the hematopoietic changes during inflammation via IL-6.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Bone Marrow / drug effects
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Bone Marrow / parasitology
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Bone Marrow / pathology
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Cell Differentiation / drug effects
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Cells, Cultured
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Colony-Forming Units Assay
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Erythroid Precursor Cells / drug effects*
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Erythroid Precursor Cells / parasitology
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Erythroid Precursor Cells / pathology
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Fibroblasts / cytology
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Fibroblasts / drug effects
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Fibroblasts / parasitology
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Hematopoiesis / drug effects
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Hematopoietic Stem Cells / drug effects
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Hematopoietic Stem Cells / parasitology
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Hematopoietic Stem Cells / pathology
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Interleukin-6 / pharmacology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Myeloid Progenitor Cells / drug effects*
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Myeloid Progenitor Cells / parasitology
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Myeloid Progenitor Cells / pathology
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Stromal Cells / drug effects*
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Stromal Cells / parasitology
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Stromal Cells / pathology
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Toxoplasma / drug effects*
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Toxoplasma / pathogenicity
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Toxoplasmosis / drug therapy*
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Toxoplasmosis / parasitology
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Toxoplasmosis / pathology