Stromal-derived IL-6 alters the balance of myeloerythroid progenitors during Toxoplasma gondii infection

David B. Chou, Brian Sworder, Nicolas Bouladoux, Cindy N. Roy, Amiko M. Uchida, Michael Grigg, Pamela G. Robey, Yasmine Belkaid

Research output: Contribution to journalArticle

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+CD146lo BM stromal fibroblasts significantly increase IL-6 secretion after infection. These data suggest that BMSCs regulate the hematopoietic changes during inflammation via IL-6.

Original languageEnglish (US)
Pages (from-to)123-131
Number of pages9
JournalJournal of Leukocyte Biology
Volume92
Issue number1
DOIs
StatePublished - Jul 2012

Keywords

  • Bone marrow stromal cell
  • Hematopoiesis
  • Inflammation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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    Chou, D. B., Sworder, B., Bouladoux, N., Roy, C. N., Uchida, A. M., Grigg, M., Robey, P. G., & Belkaid, Y. (2012). Stromal-derived IL-6 alters the balance of myeloerythroid progenitors during Toxoplasma gondii infection. Journal of Leukocyte Biology, 92(1), 123-131. https://doi.org/10.1189/jlb.1011527