Journal article
Leishmania donovani Infection Induces Anemia in Hamsters by Differentially Altering Erythropoiesis in Bone Marrow and Spleen
PloS one, Vol.8(3), pp.e59509-e59509
03/22/2013
DOI: 10.1371/journal.pone.0059509
PMCID: PMC3606219
PMID: 23533629
Abstract
Leishmania donovani is a parasite that causes visceral leishmaniasis by infecting and replicating in macrophages of the bone marrow, spleen, and liver. Severe anemia and leucopenia is associated with the disease. Although immune defense mechanisms against the parasite have been studied, we have a limited understanding of how L. donovani alters hematopoiesis. In this study, we used Syrian golden hamsters to investigate effects of L. donovani infection on erythropoiesis. Infection resulted in severe anemia and leucopenia by 8 weeks post-infection. Anemia was associated with increased levels of serum erythropoietin, which indicates the hamsters respond to the anemia by producing erythropoietin. We found that infection also increased numbers of BFU-E and CFU-E progenitor populations in the spleen and bone marrow and differentially altered erythroid gene expression in these organs. In the bone marrow, the mRNA expression of erythroid differentiation genes (alpha-globin, beta-globin, ALAS2) were inhibited by 50%, but mRNA levels of erythroid receptor (c-kit, EpoR) and transcription factors (GATA1, GATA2, FOG1) were not affected by the infection. This suggests that infection has a negative effect on differentiation of erythroblasts. In the spleen, erythroid gene expression was enhanced by infection, indicating that the anemia activates a stress erythropoiesis response in the spleen. Analysis of cytokine mRNA levels in spleen and bone marrow found that IFN-gamma mRNA is highly increased by L. donovani infection. Expression of the IFN-gamma inducible cytokine, TNF-related apoptosis-inducing ligand (TRAIL), was also up-regulated. Since TRAIL induces erythroblasts apoptosis, apoptosis of bone marrow erythroblasts from infected hamsters was examined by flow cytometry. Percentage of erythroblasts that were apoptotic was significantly increased by L. donovani infection. Together, our results suggest that L. donovani infection inhibits erythropoiesis in the bone marrow by cytokine-mediated apoptosis of erythroblasts.
Details
- Title: Subtitle
- Leishmania donovani Infection Induces Anemia in Hamsters by Differentially Altering Erythropoiesis in Bone Marrow and Spleen
- Creators
- William P. Lafuse - The Ohio State University Wexner Medical CenterRyan Story - The Ohio State University Wexner Medical CenterJocelyn Mahylis - The Ohio State University Wexner Medical CenterGaurav Gupta - The Ohio State UniversitySanjay Varikuti - The Ohio State University Wexner Medical CenterHeidi Steinkamp - The Ohio State University Wexner Medical CenterSteve Oghumu - The Ohio State University Wexner Medical CenterAbhay R. Satoskar - The Ohio State University Wexner Medical Center
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.8(3), pp.e59509-e59509
- DOI
- 10.1371/journal.pone.0059509
- PMID
- 23533629
- PMCID
- PMC3606219
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library Science
- Number of pages
- 12
- Grant note
- AI092624; AT004160 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA RC4AI092624 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) R21AT004160 / NATIONAL CENTER FOR COMPLEMENTARY &ALTERNATIVE MEDICINE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Complementary & Alternative Medicine
- Language
- English
- Date published
- 03/22/2013
- Academic Unit
- Pediatric Dentistry
- Record Identifier
- 9984367651402771
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