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

Journal of Leukocyte Biology

Amiko M. Uchida³  Yasmine Belkaid²  Michael Grigg#⁵  Brian Sworder¹  David B. Chou, ⁶  Cindy N. Roy–⁴  Nicolas Bouladoux²  Pamela G. Robey and⁵ 

[1] #Molecular Parasitology Units, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, and Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA; Graduate Program in Molecular Medicine, Boston University School of Medicine, Boston, Massachusetts, USA;Mucosal Immunology and #Molecular Parasitology Units, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, and Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA;Mucosal Immunology and #Molecular Parasitology Units, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, and Howard Hughes Medical Institute-National Institutes of Health Research Scholars Program, Bethesda, Maryland, USA Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA;#Molecular Parasitology Units, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, and –Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA;#Molecular Parasitology Units, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, and Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA;Mucosal Immunology and #Molecular Parasitology Units, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, and  University of Paris 7, Ecole Doctorale B3MI, Paris, France;

关键词: Hematopoiesis;    bone marrow stromal cell;    inflammation;   

DOI  :  10.1189/jlb.1011527

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown