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CD4(+) T Cells Alter the Stromal Microenvironment and Repress Medullary Erythropoiesis in Murine Visceral Leishmaniasis

Human visceral leishmaniasis, a parasitic disease of major public health importance in developing countries, is characterized by variable degrees of severity of anemia, but the mechanisms underlying this change in peripheral blood have not been thoroughly explored. Here, we used an experimental mode...

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Autores principales: Preham, Olivier, Pinho, Flaviane A., Pinto, Ana Isabel, Rani, Gulab Fatima, Brown, Najmeeyah, Hitchcock, Ian S., Goto, Hiro, Kaye, Paul M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305626/
https://www.ncbi.nlm.nih.gov/pubmed/30619317
http://dx.doi.org/10.3389/fimmu.2018.02958
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author Preham, Olivier
Pinho, Flaviane A.
Pinto, Ana Isabel
Rani, Gulab Fatima
Brown, Najmeeyah
Hitchcock, Ian S.
Goto, Hiro
Kaye, Paul M.
author_facet Preham, Olivier
Pinho, Flaviane A.
Pinto, Ana Isabel
Rani, Gulab Fatima
Brown, Najmeeyah
Hitchcock, Ian S.
Goto, Hiro
Kaye, Paul M.
author_sort Preham, Olivier
collection PubMed
description Human visceral leishmaniasis, a parasitic disease of major public health importance in developing countries, is characterized by variable degrees of severity of anemia, but the mechanisms underlying this change in peripheral blood have not been thoroughly explored. Here, we used an experimental model of visceral leishmaniasis in C57BL/6 mice to explore the basis of anemia following infection with Leishmania donovani. 28 days post-infection, mice showed bone marrow dyserythropoiesis by myelogram, with a reduction of TER119(+) CD71(−/+) erythroblasts. Reduction of medullary erythropoiesis coincided with loss of CD169(high) bone marrow stromal macrophages and a reduction of CXCL12-expressing stromal cells. Although the spleen is a site of extramedullary erythropoiesis and erythrophagocytosis, splenectomy did not impact the extent of anemia or affect the repression of medullary hematopoiesis that was observed in infected mice. In contrast, these changes in bone marrow erythropoiesis were not evident in B6.Rag2(−/−) mice, but could be fully reconstituted by adoptive transfer of IFNγ-producing but not IFNγ-deficient CD4(+) T cells, mimicking the expansion of IFNγ-producing CD4(+) T cells that occurs during infection in wild type mice. Collectively, these data indicate that anemia during experimental murine visceral leishmaniasis can be driven by defects associated with the bone marrow erythropoietic niche, and that this represents a further example of CD4(+) T cell-mediated immunopathology affecting hematopoietic competence.
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spelling pubmed-63056262019-01-07 CD4(+) T Cells Alter the Stromal Microenvironment and Repress Medullary Erythropoiesis in Murine Visceral Leishmaniasis Preham, Olivier Pinho, Flaviane A. Pinto, Ana Isabel Rani, Gulab Fatima Brown, Najmeeyah Hitchcock, Ian S. Goto, Hiro Kaye, Paul M. Front Immunol Immunology Human visceral leishmaniasis, a parasitic disease of major public health importance in developing countries, is characterized by variable degrees of severity of anemia, but the mechanisms underlying this change in peripheral blood have not been thoroughly explored. Here, we used an experimental model of visceral leishmaniasis in C57BL/6 mice to explore the basis of anemia following infection with Leishmania donovani. 28 days post-infection, mice showed bone marrow dyserythropoiesis by myelogram, with a reduction of TER119(+) CD71(−/+) erythroblasts. Reduction of medullary erythropoiesis coincided with loss of CD169(high) bone marrow stromal macrophages and a reduction of CXCL12-expressing stromal cells. Although the spleen is a site of extramedullary erythropoiesis and erythrophagocytosis, splenectomy did not impact the extent of anemia or affect the repression of medullary hematopoiesis that was observed in infected mice. In contrast, these changes in bone marrow erythropoiesis were not evident in B6.Rag2(−/−) mice, but could be fully reconstituted by adoptive transfer of IFNγ-producing but not IFNγ-deficient CD4(+) T cells, mimicking the expansion of IFNγ-producing CD4(+) T cells that occurs during infection in wild type mice. Collectively, these data indicate that anemia during experimental murine visceral leishmaniasis can be driven by defects associated with the bone marrow erythropoietic niche, and that this represents a further example of CD4(+) T cell-mediated immunopathology affecting hematopoietic competence. Frontiers Media S.A. 2018-12-18 /pmc/articles/PMC6305626/ /pubmed/30619317 http://dx.doi.org/10.3389/fimmu.2018.02958 Text en Copyright © 2018 Preham, Pinho, Pinto, Rani, Brown, Hitchcock, Goto and Kaye. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Preham, Olivier
Pinho, Flaviane A.
Pinto, Ana Isabel
Rani, Gulab Fatima
Brown, Najmeeyah
Hitchcock, Ian S.
Goto, Hiro
Kaye, Paul M.
CD4(+) T Cells Alter the Stromal Microenvironment and Repress Medullary Erythropoiesis in Murine Visceral Leishmaniasis
title CD4(+) T Cells Alter the Stromal Microenvironment and Repress Medullary Erythropoiesis in Murine Visceral Leishmaniasis
title_full CD4(+) T Cells Alter the Stromal Microenvironment and Repress Medullary Erythropoiesis in Murine Visceral Leishmaniasis
title_fullStr CD4(+) T Cells Alter the Stromal Microenvironment and Repress Medullary Erythropoiesis in Murine Visceral Leishmaniasis
title_full_unstemmed CD4(+) T Cells Alter the Stromal Microenvironment and Repress Medullary Erythropoiesis in Murine Visceral Leishmaniasis
title_short CD4(+) T Cells Alter the Stromal Microenvironment and Repress Medullary Erythropoiesis in Murine Visceral Leishmaniasis
title_sort cd4(+) t cells alter the stromal microenvironment and repress medullary erythropoiesis in murine visceral leishmaniasis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305626/
https://www.ncbi.nlm.nih.gov/pubmed/30619317
http://dx.doi.org/10.3389/fimmu.2018.02958
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