HIV and immunity to malaria

在非洲，恶性疟疾和艾滋病毒感染是毁灭性的健康问题，艾滋病毒使疟疾恶化，特别是在怀孕期间。最近，我们展示了为什么会出现这种情况。在怀孕期间，针对疟疾感染细胞表面表达的蛋白质的抗体可以保护胎盘免受疟疾的侵袭。这些抗体的水平随着艾滋病毒感染而降低，在患有艾滋病的妇女中最低。第一次怀孕的母亲和有经验的母亲都缺乏抗体。现在我们将研究这些抗体的功能。它们可能会阻止与胎盘受体的粘连，减少胎盘中的寄生虫数量。或者，它们可能包裹受感染的红细胞，使其成为巨噬细胞(白血球)吞噬(吞噬)的目标。我们将检查艾滋病毒对每个过程的影响，以找出抗体降低可能如何影响孕妇。艾滋病毒还影响巨噬细胞和相关免疫细胞、单核细胞和树突状细胞。我们将研究这些细胞中的艾滋病毒感染如何损害它们吃掉疟疾细胞的方式，以及当它们遇到疟疾时，它是否改变了它们被激活并产生抗感染蛋白的方式。如果没有这些蛋白质，疟疾可能会肆无忌惮地发展。使用我们的新分析方法，我们将研究非洲妇女的这些反应。我们将发现艾滋病毒是否也会影响感染疟疾风险最高的儿童的寄生虫表达的蛋白质抗体。艾滋病毒尤其会减少对新靶点的抗体产生，因此几乎没有疟疾经历的儿童可能缺乏对许多不同蛋白质的抗体。我们将找出儿童中疟疾抗体水平低是否可能是导致儿童患上更严重疟疾的原因。通过了解艾滋病毒如何影响疟疾免疫，我们可以开发更好的方法来保护面临疟疾风险的人。这些发现对疟疾疫苗的研究也将是重要的。如果HIV感染者对自然感染的反应很差，他们也可能对疫苗没有反应。

In Africa, Plasmodium falciparum malaria and HIV infection are devastating health problems, and HIV makes malaria worse, especially in pregnancy. Recently, we showed why this may be. In pregnancy, antibodies to proteins expressed on the surface of malaria infected cells protect against malaria in the placenta. Levels of these antibodies were decreased by HIV infection, and lowest in women with AIDS. Both first-time and experienced mothers lacked antibody. Now we will investigate the function of these antibodies. They might block adhesion to placental receptors, decreasing parasite numbers in the placenta. Or they might coat infected red cells, making them targets for phagocytosis (eating) by macrophages (white blood cells). We will examine the effects of HIV on each process, to find out how reduced antibody might affect the pregnant woman. HIV also affects macrophages and related immune cells, monocytes and dendritic cells. We will study how HIV infection in these cells impairs the way they eat malaria cells, and whether it alters the way they become activated and produce infection-fighting proteins when they encounter malaria. Without these proteins, malaria may grow unchallenged. Using our new assays we will study these responses in African women. We will discover whether HIV also affects antibodies to proteins expressed by parasites infecting children, who are at highest risk of malaria. HIV particularly decreases development of antibody to new targets, so children with little malaria experience may lack antibodies to many different proteins. We will find out whether low levels of malaria antibody in children may be the reason why the get more severe malaria. By understanding how HIV affects malaria immunity, we can develop better ways to protect people at risk from malaria. These findings will also be important to work on malaria vaccines. If HIV infected people respond poorly to natural infection, they may also fail to respond to vaccines.