The severity of malarial anaemia in Plasmodium chabaudi infections of BALB/c mice is determined independently of the number of circulating parasites
The severity of malarial anaemia in Plasmodium chabaudi infections of BALB/c mice is determined independently of the number of circulating parasites
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DOI：
10.1186/1475-2875-7-68
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发表时间：
2008-04-25
期刊：
影响因子：
3
通讯作者：
Langhorne, Jean
中科院分区：
文献类型：
--
作者：
Lamb, Tracey J.;Langhorne, Jean
背景：严重疟疾贫血是疟疾感染的主要并发症，是由寄生虫复制造成的循环红细胞（rbc）损失以及免疫介导机制引起的多因素。了解严重疟疾贫血的原因对于制定和实施新的治疗战略以应对这种疟疾感染综合征是必要的。方法：采用方差分析方法，研究BALB/c背景小鼠感染啮齿动物疟疾模型chabaudi疟原虫时，疟原虫对红细胞的破坏是否总是导致疟疾贫血的严重程度。还研究了两个不同克隆间的贫血差异。结果：循环寄生虫数量与BALB/c小鼠或更严重的BALB/c RAG2缺陷小鼠（缺乏T和B细胞）贫血的严重程度无关。感染chabaudi P.克隆CB的小鼠比感染克隆AS的小鼠出现更严重的贫血，但这与循环中寄生虫的数量无关。相反，被寄生红细胞的峰值百分比在cb感染的动物中高于as感染的动物，并且与贫血的严重程度相关，这表明未感染红细胞的可用性在cb感染的动物中受损。结论：本研究表明，与不考虑贫血的%寄生虫血症相比，寄生虫数量是衡量chabaudi感染中寄生虫水平的一个更相关的指标。在该疟疾实验模型中，寄生虫数量与循环红细胞下降之间缺乏相关性，这支持了宿主反应在恰巴迪疟原虫感染中未感染红细胞的损伤或破坏中的作用，从而在该疟疾模型中发展为急性贫血。
Background: Severe malarial anaemia is a major complication of malaria infection and is multifactorial resulting from loss of circulating red blood cells (RBCs) from parasite replication, as well as immune-mediated mechanisms. An understanding of the causes of severe malarial anaemia is necessary to develop and implement new therapeutic strategies to tackle this syndrome of malaria infection.Methods: Using analysis of variance, this work investigated whether parasite-destruction of RBCs always accounts for the severity of malarial anaemia during infections of the rodent malaria model Plasmodium chabaudi in mice of a BALB/c background. Differences in anaemia between two different clones of P. chabaudi were also examined.Results: Circulating parasite numbers were not correlated with the severity of anaemia in either BALB/c mice or under more severe conditions of anaemia in BALB/c RAG2 deficient mice (lacking T and B cells). Mice infected with P. chabaudi clone CB suffered more severe anaemia than mice infected with clone AS, but this was not correlated with the number of parasites in the circulation. Instead, the peak percentage of parasitized RBCs was higher in CB-infected animals than in AS-infected animals, and was correlated with the severity of anaemia, suggesting that the availability of uninfected RBCs was impaired in CB-infected animals.Conclusion: This work shows that parasite numbers are a more relevant measure of parasite levels in P. chabaudi infection than % parasitaemia, a measure that does not take anaemia into account. The lack of correlation between parasite numbers and the drop in circulating RBCs in this experimental model of malaria support a role for the host response in the impairment or destruction of uninfected RBC in P. chabaudi infections, and thus development of acute anaemia in this malaria model.