CD4+ T cells participate in the nephropathy of canine visceral leishmaniasis

F.A.L. Costa, J.L. Guerra, S.M.M.S. Silva, R.P. Klein, I.L. Mendonça, H. Goto
2000 Brazilian Journal of Medical and Biological Research  
0000-0002-9640-6333 et al. (5 more authors) (2018) CD4+ 1 T cells alter the stromal microenvironment and repress medullary erythropoiesis in murine visceral leishmaniasis. Frontiers in immunology. 2958. ISSN 1664-3224 https://doi.org/10.3389/fimmu.2018.02958 eprints@whiterose.ac.uk https://eprints.whiterose.ac.uk/ Reuse This article is distributed under the terms of the Creative Commons Attribution (CC BY) licence. This licence allows you to distribute, remix, tweak, and build upon the work,
more » ... d upon the work, even commercially, as long as you credit the authors for the original work. More information and the full terms of the licence here: https://creativecommons.org/licenses/ Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request. Abstract 22 Human visceral leishmaniasis, a parasitic disease of major public health importance in 23 developing countries, is characterized by variable degrees of severity of anemia, but the 24 mechanisms underlying this change in peripheral blood have not been thoroughly explored. 25 Here, we used an experimental model of visceral leishmaniasis in C57BL/6 mice to explore 26 the basis of anemia following infection with Leishmania donovani. 28 days post infection, 27 mice showed bone marrow dyserythropoiesis by myelogram, with a reduction of TER119 + 28 CD71 -/+ erythroblasts. Reduction of medullary erythropoiesis coincided with loss of 29 CD169 high bone marrow stromal macrophages and a reduction of CXCL12-expressing 30 stromal cells. Although the spleen is a site of extramedullary erythropoiesis and 31 erythrophagocytosis, splenectomy did not impact the extent of anemia or affect the repression 32 of medullary hematopoiesis that was observed in infected mice. In contrast, these changes in 33 bone marrow erythropoiesis were not evident in B6.Rag2 -/mice, but could be fully 34 reconstituted by adoptive transfer of IFNg-producing but not IFNg-deficient CD4 + T cells, 35 mimicking the expansion of IFNg-producing CD4 + T cells that occurs during infection in 36 wild type mice. Collectively, these data indicate that anemia during experimental murine 37 visceral leishmaniasis can be driven by defects associated with the bone marrow 38 erythropoietic niche, and that this represents a further example of CD4 + T cell-mediated 39 immunopathology affecting hematopoietic competence. 40 41 42 3
doi:10.1590/s0100-879x2000001200009 pmid:11105098 fatcat:tkuvl2xmrjaz7nv2iwvdqpr6gq