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

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Arquivos
art_PREHAM_CD4_T_Cells_Alter_the_Stromal_Microenvironment_and_2018.PDF (3.53 MB)
Citações na Scopus
16
Tipo de produção
article
Data de publicação
2018
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
FRONTIERS MEDIA SA
Autores
PREHAM, Olivier
PINHO, Flaviane A.
PINTO, Ana Isabel
RANI, Gulab Fatima
BROWN, Najmeeyah
HITCHCOCK, Ian S.
KAYE, Paul M.
Citação
FRONTIERS IN IMMUNOLOGY, v.9, article ID 2958, 12p, 2018
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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 IFN gamma-producing but not IFN gamma-deficient CD4(+) T cells, mimicking the expansion of IFN gamma-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.
Palavras-chave
erythropoiesis, stromal cells, macrophages, bone marrow, leishmaniasis
URI
https://observatorio.fm.usp.br/handle/OPI/30030
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MPR
Artigos e Materiais de Revistas Científicas - LIM/38