Preham, O;
Pinho, FA;
Pinto, AI;
Rani, GF;
Brown, N;
Hitchcock, IS;
Goto, H;
(2018)
CD4^{+} T Cells Alter the Stromal Microenvironment and Repress Medullary Erythropoiesis in Murine Visceral Leishmaniasis.
Frontiers in Immunology
, 9
, Article 2958. 10.3389/fimmu.2018.02958.
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Abstract
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^{+} CD716^{-/+} 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.
| Type: | Article |
|---|---|
| Title: | CD4^{+} T Cells Alter the Stromal Microenvironment and Repress Medullary Erythropoiesis in Murine Visceral Leishmaniasis |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fimmu.2018.02958 |
| Publisher version: | http://doi.org/10.3389/fimmu.2018.02958 |
| Language: | English |
| Additional information: | © 2018 Preham, Pinho, Pinto, Rani, Brown, Hitchcock, Goto and Kaye. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | erythropoiesis, stromal cells, macrophages, bone marrow, leishmaniasis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10074474 |
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