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Comparative Study
. 2018 Jan 9;17(1):18.
doi: 10.1186/s12936-017-2159-3.

Differential induction of malaria liver pathology in mice infected with Plasmodium chabaudi AS or Plasmodium berghei NK65

Affiliations
Comparative Study

Differential induction of malaria liver pathology in mice infected with Plasmodium chabaudi AS or Plasmodium berghei NK65

Diletta Scaccabarozzi et al. Malar J. .

Abstract

Background: Cerebral malaria and severe anaemia are the most common deadly complications of malaria, and are often associated, both in paediatric and adult patients, with hepatopathy, whose pathogenesis is not well characterized, and sometimes also with acute respiratory distress syndrome (ARDS). Here, two species of murine malaria, the lethal Plasmodium berghei strain NK65 and self-healing Plasmodium chabaudi strain AS which differ in their ability to cause hepatopathy and/or ARDS were used to investigate the lipid alterations, oxidative damage and host immune response during the infection in relation to parasite load and accumulation of parasite products, such as haemozoin. VSports手机版.

Methods: Plasma and livers of C57BL/6J mice injected with PbNK65 or PcAS infected erythrocytes were collected at different times and tested for parasitaemia, content of haemozoin and expression of tumour necrosis factor (TNF) V体育安卓版. Hepatic enzymes, antioxidant defenses and lipids content and composition were also evaluated. .

Results: In the livers of P. berghei NK65 infected mice both parasites and haemozoin accumulated to a greater extent than in livers of P. chabaudi AS infected mice although in the latter hepatomegaly was more prominent. Hepatic enzymes and TNF were increased in both models. Moreover, in P. berghei NK65 infected mice, increased lipid peroxidation, accumulation of triglycerides, impairment of anti-oxidant enzymes and higher collagen deposition were detected. On the contrary, in P. chabaudi AS infected mice the antioxidant enzymes and the lipid content and composition were normal or even lower than uninfected controls. V体育ios版.

Conclusions: This study demonstrates that in C57BL/6J mice, depending on the parasite species, malaria-induced liver pathology results in different manifestations, which may contribute to the different outcomes. In P. berghei NK65 infected mice, which concomitantly develop lethal acute respiratory distress syndrome, the liver tissue is characterized by an excess oxidative stress response and reduced antioxidant defenses while in P. chabaudi AS infected mice hepatopathy does not lead to lipid alterations or reduction of antioxidant enzymes, but rather to inflammation and cytokine burst, as shown earlier, that may favour parasite killing and clearance of the infection. These results may help understanding the different clinical profiles described in human malaria hepatopathy. VSports最新版本.

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Figures

Fig. 1
Fig. 1
Disease course in mice infected with P. berghei NK65 or P. chabaudi AS. C57BL/6J mice were injected intraperitoneally with 104 erythrocytes infected with P. berghei (PbNK65) or P. chabaudi AS (PcAS). Peripheral parasitaemia (a) and weights of the livers (b) were determined at day 8 and 10 post infection. n = 15–16 mice for each time point and strain. Data are pooled from three different experiments performed in the same conditions. **p < 0.01; vs control; °p < 0.05 P. berghei NK65 vs P. chabaudi AS
Fig. 2
Fig. 2
Hepatic haemozoin levels, oxidative damage and fibrosis in liver tissue of P. berghei NK65 or P. chabaudi AS infected mice. Hz content in liver tissue (pmol Hz/mg liver tissue) of P. berghei NK65 or P. chabaudi AS infected C57Bl/6J mice at day 8 and 10 post infection (a). Hepatic mRNA expression levels of TNF-α in non-infected and infected mice at day 8 or day 10 post infection determined by quantitative RT-PCR and normalized to 18S ribosomal RNA levels (b). OH-proline content (μg/mg protein) in non-infected and infected mice at day 8 or day 10 post infection (c); MDA content (pmol/liver) in non-infected and infected mice at day 8 or day 10 post infection (d). n = 6 mice/for each time point and group. *p < 0.05; **p < 0.01; ***p < 0.0001 vs Control; °°p < 0.05; °°°p < 0.01 P. berghei NK65 vs P. chabaudi AS
Fig. 3
Fig. 3
Enzymes activity in the liver of C57Bl/6J mice infected by P. berghei NK65 or P. chabaudi AS. Catalase activity (a), total GSH (b), SOD activity (c) and glutathione reductase activity (d) were determined in the livers of non-infected and infected mice at day 8 and day 10 post infection. n = 8 mice/group. Data are from one representative experiment out of three performed in the same conditions; *p < 0.05; **p < 0.01; ***p < 0.0001 vs control
Fig. 4
Fig. 4
Alteration in the lipid profiles of the livers from uninfected, P. berghei NK65 or P. chabaudi AS infected mice. Mice infected with P. berghei NK65 or P. chabaudi AS were dissected at day 8 and 10 post infection. The total content of liver triglycerides (TG) and phospholipids (PL) were determined as described in “Methods” (a and c). The content of ChoE and free Cho is shown in b and d, respectively. n = 8 mice for each condition. Data are from one representative experiment out of three performed in the same conditions *p < 0.05; **p < 0.01; ***p < 0.0001 vs Control; °p < 0.05; °°°p < 0.001 P. berghei NK65 vs P. chabaudi AS
Fig. 5
Fig. 5
Phospholipids composition in liver from uninfected, P. berghei NK65 or P. chabaudi AS infected mice. The distribution of liver PL (µg PL/mg protein) was determined in uninfected and in P. berghei NK65- or P. chabaudi AS-infected mice at day 8 or 10 post infection. Data are from one representative experiment out of three performed in the same conditions. LPC lysophosphatidylcholine, SM sphingomyelin, PC phosphatidylcholine, PS phosphatidylserine, PI phosphatidylinositol, PE phosphatidylethanolamine, CD cardiolipine

References

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