Plasmodium strain determines dendritic cell function essential for survival from malaria.
Plasmodium strain determines dendritic cell function essential for survival from malaria.
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疟原虫菌株决定了疟疾生存至关重要的树突状细胞功能。
DOI：
10.1371/journal.ppat.0030096
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发表时间：
2007-07
期刊：
影响因子：
6.7
通讯作者：
Good, Michael F
中科院分区：
文献类型：
--
作者：
Wykes, Michelle N;Liu, Xue Q;Beattie, Lynette;Stanisic, Danielle I;Stacey, Katryn J;Smyth, Mark J;Thomas, Ranjeny;Good, Michael F
疟疾的严重程度可从无症状到致命感染，包括严重贫血和脑病。然而，导致这些疾病严重程度差异的分子和细胞因素却知之甚少。确定介导毒力的因素将有助于发展抗寄生虫免疫反应。由于免疫是由树突状细胞（dc）启动的，我们比较了它们在感染非致死性或致死性约氏疟原虫（Plasmodium yoelii）后的表型和功能，以确定它们对疾病严重程度的贡献。来自非致死性感染的树突状细胞功能齐全，能够分泌细胞因子并刺激T细胞。相比之下，来自致命感染的dc没有功能。然后，我们将非致死性感染小鼠的dc转移到致死性感染小鼠中，并发现这些dc介导了寄生虫血症和存活的控制。IL-12是生存所必需的。据我们所知，我们的研究首次表明，在疟疾感染期间，DC功能对生存至关重要。更重要的是，这些dc的功能是由寄生虫的品系决定的。我们的研究可以部分解释为什么自然疟疾感染可能会有不同的结果。疟疾是一种复杂的疾病，关于为什么疟原虫感染具有从无症状到致命感染的不同结果的数据很少。由于免疫是由树突状细胞（DC）启动的，一些研究调查了DC在疟疾期间的功能。目前关于感染对DC功能影响的数据尚无定论，一种观点认为DC功能正常，另一种观点认为DC功能受损。然而，这些研究使用了不同种类和菌株的疟原虫。我们比较了致死性和非致死性感染期间的DC功能，发现了显著差异。我们的研究表明，寄生虫的菌株决定了dc在感染后是否保持功能。此外，通过在小鼠之间转移DC，我们发现DC功能对于从致命感染中存活是必不可少的。这项研究为当前的争议提供了一些见解，并为疾病严重程度的差异提供了一个合理的解释。
The severity of malaria can range from asymptomatic to lethal infections involving severe anaemia and cerebral disease. However, the molecular and cellular factors responsible for these differences in disease severity are poorly understood. Identifying the factors that mediate virulence will contribute to developing antiparasitic immune responses. Since immunity is initiated by dendritic cells (DCs), we compared their phenotype and function following infection with either a nonlethal or lethal strain of the rodent parasite, Plasmodium yoelii, to identify their contribution to disease severity. DCs from nonlethal infections were fully functional and capable of secreting cytokines and stimulating T cells. In contrast, DCs from lethal infections were not functional. We then transferred DCs from mice with nonlethal infections to mice given lethal infections and showed that these DCs mediated control of parasitemia and survival. IL-12 was necessary for survival. To our knowledge, our studies have shown for the first time that during a malaria infection, DC function is essential for survival. More importantly, the functions of these DCs are determined by the strain of parasite. Our studies may explain, in part, why natural malaria infections may have different outcomes. Malaria is a complex disease and there is little data on why Plasmodium infections have different outcomes that can range from asymptomatic to lethal infections. Since immunity is initiated by dendritic cells (DCs), several studies have investigated DC function during malaria. Current data on the effects of infection on DC functions are inconclusive, with one school of thought being that DC function is normal and the other that DC function is compromised. However, these studies have used different species and strains of Plasmodium. We have compared DC function during a lethal and nonlethal infection and found significant differences. Our study shows that the strain of parasite determines if DCs remain functional following infection. Moreover, by transferring DCs between mice, we show that DC function is essential for survival from a lethal infection. This study offers some insight into the current controversy and offers a plausible explanation for differences in the severity of disease.