Anemia in Experimental Visceral Leishmaniasis in Hamsters

Biswas, Tanmay; Chakraborty, Mummun; Naskar, Khudiram; Ghosh, Dilip K.; Ghosal, Jharna

doi:10.2307/3283701

Cited by 11 publications

(8 citation statements)

References 13 publications

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“…Anemia, a characteristic trait in L. infantum infected humans, dogs and laboratory rodents [33]–[35], was not observed in the L. infantum infected T. laurentius . Although animals infected by L. infantum displayed a significant decrease of the hematological parameters in comparison to those infected with L. braziliensis , this decrease still did not characterize anemia.…”

Section: Discussionmentioning

confidence: 86%

Thrichomys laurentius (Rodentia; Echimyidae) as a Putative Reservoir of Leishmania infantum and L. braziliensis: Patterns of Experimental Infection

Roque

Cupolillo

Marchevsky³

et al. 2010

PLoS Negl Trop Dis

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The importance of the genus Thrichomys in the retention of infection and transmission of Leishmania species is supported by previous studies that describe an ancient interaction between caviomorphs and trypanosomatids and report the natural infection of Thrichomys spp. Moreover, these rodents are widely dispersed in Brazil and recognized as important hosts of other tripanosomatids. Our main purpose was to evaluate the putative role of Thrichomys laurentius in the retention of infection and amplification of the transmission cycle of Leishmania infantum and L. braziliensis. Male and female T. laurentius (n = 24) born in captivity were evaluated for the retention of infection with these Leishmania species and followed up by parasitological, serological, hematological, biochemical, histological, and molecular assays for 3, 6, 9, or 12 months post infection (mpi). T. laurentius showed its competence as maintenance host for the two inoculated Leishmania species. Four aspects should be highlighted: (i) re-isolation of parasites 12 mpi; (ii) the low parasitic burden displayed by T. laurentius tissues; (iii) the early onset and maintenance of humoral response, and (iv) the similar pattern of infection by the two Leishmania species. Both Leishmania species demonstrated the ability to invade and maintain itself in viscera and skin of T. laurentius, and no rodent displayed any lesion, histological changes, or clinical evidence of infection. We also wish to point out the irrelevance of the adjective dermotropic or viscerotropic to qualify L. braziliensis and L. infantum, respectively, when these species are hosted by nonhuman hosts. Our data suggest that T. laurentius may act at least as a maintenance host of both tested Leishmania species since it maintained long-lasting infections. Moreover, it cannot be discarded that Leishmania spp. infection in free-ranging T. laurentius could result in higher parasite burden due the more stressing conditions in the wild. Therefore the tissular parasitism of the skin, infectiveness to the vector, and amplification of the transmission cycle of both Leishmania species could be expected.

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Section: Discussionmentioning

confidence: 86%

Thrichomys laurentius (Rodentia; Echimyidae) as a Putative Reservoir of Leishmania infantum and L. braziliensis: Patterns of Experimental Infection

Roque

Cupolillo

Marchevsky³

et al. 2010

PLoS Negl Trop Dis

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“…Hamsters infected with L. donovani develop a progressive disease in which uncontrolled parasite growth in the spleen and liver results in hepatosplenomegaly, anemia, leucopenia, and eventually death [21]–[24]. In the current study, hamsters were infected with 10 9 amastigotes by intraperitoneal injection and disease assessed at 8 weeks post infection.…”

Section: Resultsmentioning

confidence: 94%

Leishmania donovani Infection Induces Anemia in Hamsters by Differentially Altering Erythropoiesis in Bone Marrow and Spleen

et al. 2013

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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 (α-globin, β-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-γ mRNA is highly increased by L. donovani infection. Expression of the IFN-γ 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.

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“…Elevation of intracellular Ca 2 1 concentration, leading to cumulative membrane damage, has been seen in the erythrocytes of those with sickle cell anaemia, b -thalassaemia or malaria (Eaton et al, 1973;Palek, 1973;Mohan et al, 1994). In hamsters infected with Leishmania donovani, an enhancement of lipid peroxidation in the erythrocytes, along with signi® cant degradation of both the cytoskeletal and integral membrane proteins, was evident as anaemia developed (Biswas et al, 1992(Biswas et al, , 1995. Recent observations on the contribution of oxidative stress to increased intracellu lar Ca 2 1 concentrations in senescent cells (Aiken et al, 1995) led to the present investigation, of the role of Ca 2 1 in the proteolytic degradation of the membrane proteins of erythrocytes during L. donovani infection in hamsters.…”

mentioning

confidence: 99%

Altered calcium homeostasis and membrane destabilization in erythrocytes of hamsters infected with Leishmania donovani

Sen

Ghosal

Naskar

et al. 2000

Annals of Tropical Medicine And Parasitology

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Homeostatic mechanisms regulating intracellular concentrations of Ca2+ at a low level are prerequisites for maintaining the integral and cytoskeletal structure of erythrocytes under normal physiological conditions. The present study was undertaken to assess the contribution of Ca2+ homeostasis in modifying red-cell stability in hamsters, during the anaemia caused by Leishmania donovani. Erythrocytes from the infected animals became increasingly fragile as infection progressed. This fragility may be the result of a gradual change in membrane permeability, as indicated by enhanced uptake of 45Ca2+. The increase in cytosolic Ca2+ and decrease in membrane-bound Ca2+ observed indicate the release of Ca2+ from the membrane store, leading to [Ca2+]i accumulation in the later stages of the post-infection period. Decline in the efficacy of Ca(2+)-effluxing enzyme may also contribute to the enhanced [Ca2+]i level, with subsequent degradation of membrane proteins in the erythrocytes of the infected animals. Marked inhibition of proteolytic degradation by the Ca(2+)-dependent thiol protease inhibitor leupeptin, with concomitant thiol depletion, indicates the involvement of Ca(2+)-induced thiol protease in the observed degradation of membrane proteins. The results indicate that an altered Ca2+ homeostasis in erythrocytes following leishmanial infection causes enhanced cellular accumulation of Ca2+, which in turn may lead to haemolysis in experimental visceral leishmaniasis.

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Anemia in Experimental Visceral Leishmaniasis in Hamsters

Cited by 11 publications

References 13 publications

Thrichomys laurentius (Rodentia; Echimyidae) as a Putative Reservoir of Leishmania infantum and L. braziliensis: Patterns of Experimental Infection

Thrichomys laurentius (Rodentia; Echimyidae) as a Putative Reservoir of Leishmania infantum and L. braziliensis: Patterns of Experimental Infection

Leishmania donovani Infection Induces Anemia in Hamsters by Differentially Altering Erythropoiesis in Bone Marrow and Spleen

Altered calcium homeostasis and membrane destabilization in erythrocytes of hamsters infected with Leishmania donovani

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