Mechanism of malaria parasite adhesion

在非洲，恶性疟原虫疟疾感染对儿童和孕妇的影响最大。感染疟疾的红细胞粘附在血管内壁细胞的受体分子上。这种寄生虫产生一种叫做PfEMP1的蛋白质家族，在细胞表面表达。这些PfEMP1蛋白负责粘附，是宿主对疟疾免疫反应的主要目标。我们已经发现了两种特殊的受体分子，即硫酸软骨素A （CSA）和透明质酸（HA），它们在粘附在胎盘上特别重要，并且已经确定了一种附着在这些受体分子上的PfEMP1分子。我们将研究针对寄生虫的抗体，以及针对CSA和HA分子的抗体在预防疟疾中的作用。我们认为，非洲妇女随着怀孕次数的增加而产生这些抗体，保护她们自己和她们的婴儿在以后的怀孕中免受疟疾的侵害，而男性则不会产生这些抗体。感染艾滋病毒/艾滋病的孕妇更容易感染疟疾。我们将比较HIV+和HIV-女性的抗体反应，看看这是否是因为她们产生的保护性抗体较少。PfEMP1蛋白是多种基因的产物。我们可以用它们表达的var基因来比较它们。我们将检查来自不同患者的寄生虫的var基因表达，以及血液中循环或卡在胎盘（孕妇）或脑，肺，肠道和其他器官（死于疟疾的儿童）中的寄生虫，看看var基因表达的指纹在这些不同的患者之间，或者在同一患者的不同部位之间是否存在差异。

The greatest impact of Plasmodium falciparum malaria infection in Africa is on children and pregnant women. Malaria infected red blood cells stick to receptor molecules on cells lining blood vessels. The parasite produces a family of proteins called PfEMP1, expressed on the cell surface. These PfEMP1 proteins are responsible for the sticking, and are major targets of the host immune response to malaria. We have found two particular receptor molecules, sugars called chondroitin sulphate A (CSA) and hyaluronic acid (HA), to be particularly important in sticking in the placenta, and have identified a PfEMP1 molecule which sticks to these. We will study the role of antibodies against the parasite, and against the CSA and HA molecules, in protection against malaria. We believe that African women develop these antibodies with increasing pregnancies, protecting themselves and their babies from malaria in later pregnancies, and that men will not have these antibodies. Pregnant women who have HIV-AIDS have greater susceptiblity to malaria. We will compare antibody responses in HIV+ and HIV- women to see if this is because they produce less protective antibodies. The PfEMP1 proteins are the product of var genes. We can compare parasites using the var genes they express to fingerprint them. We will examine the var gene expression by parasites from different patients, and by the parasites circulating in the blood or stuck in the placenta (in pregnant women) or in the brain, lung, gut and other organs (of children who have died of malaria) to see if the fingerprints of var gene expression differ between these different patients, or between different places in the same patient.