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.

journal_name

J Leukoc Biol

authors

Chou DB,Sworder B,Bouladoux N,Roy CN,Uchida AM,Grigg M,Robey PG,Belkaid Y

doi

10.1189/jlb.1011527

subject

Has Abstract

pub_date

2012-07-01 00:00:00

pages

123-31

issue

1

eissn

0741-5400

issn

1938-3673

pii

jlb.1011527

journal_volume

92

pub_type

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