Document Detail

Stromal-derived IL-6 alters the balance of myeloerythroid progenitors during Toxoplasma gondii infection.
MedLine Citation:
PMID:  22493080     Owner:  NLM     Status:  MEDLINE    
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.
David B Chou; Brian Sworder; Nicolas Bouladoux; Cindy N Roy; Amiko M Uchida; Michael Grigg; Pamela G Robey; Yasmine Belkaid
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-04-09
Journal Detail:
Title:  Journal of leukocyte biology     Volume:  92     ISSN:  1938-3673     ISO Abbreviation:  J. Leukoc. Biol.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-06-29     Completed Date:  2012-09-05     Revised Date:  2013-07-02    
Medline Journal Info:
Nlm Unique ID:  8405628     Medline TA:  J Leukoc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  123-31     Citation Subset:  IM    
Mucosal Immunology, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
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MeSH Terms
Bone Marrow / drug effects,  parasitology,  pathology
Cell Differentiation / drug effects
Cells, Cultured
Colony-Forming Units Assay
Erythroid Precursor Cells / drug effects*,  parasitology,  pathology
Fibroblasts / cytology,  drug effects,  parasitology
Hematopoiesis / drug effects
Hematopoietic Stem Cells / drug effects,  parasitology,  pathology
Interleukin-6 / pharmacology*
Mice, Inbred C57BL
Mice, Knockout
Myeloid Progenitor Cells / drug effects*,  parasitology,  pathology
Stromal Cells / drug effects*,  parasitology,  pathology
Toxoplasma / drug effects*,  pathogenicity
Toxoplasmosis / drug therapy*,  parasitology,  pathology
Grant Support
R01 DK082722/DK/NIDDK NIH HHS; //Howard Hughes Medical Institute
Reg. No./Substance:

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