title: Stromal-derived IL-6 alters the balance of myeloerythroid progenitors during Toxoplasma gondii infection.
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.
authors.affiliation: Mucosal Immunology, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Chou
authors.forename: Brian
authors.initials: B
authors.lastname: Sworder
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bouladoux
authors.forename: Cindy N
authors.initials: CN
authors.lastname: Roy
authors.forename: Amiko M
authors.initials: AM
authors.lastname: Uchida
authors.forename: Michael
authors.initials: M
authors.lastname: Grigg
authors.forename: Pamela G
authors.initials: PG
authors.lastname: Robey
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Belkaid
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000469:parasitology / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D015672:Erythroid Precursor Cells / Q000187:drug effects* / Q000469:parasitology / Q000473:pathology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000469:parasitology; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000469:parasitology / Q000473:pathology; D015850:Interleukin-6 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023461:Myeloid Progenitor Cells / Q000187:drug effects* / Q000469:parasitology / Q000473:pathology; D017154:Stromal Cells / Q000187:drug effects* / Q000469:parasitology / Q000473:pathology; D014122:Toxoplasma / Q000187:drug effects* / Q000472:pathogenicity; D014123:Toxoplasmosis / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology
chemical_list: D015850:Interleukin-6