The role of heme oxygenase-1 in malaria-induced immunomodulation

疟疾是一种热带疾病，它本身就能杀人，并削弱对其他感染的免疫防御。感染疟疾的儿童对疫苗接种的反应较低，更容易受到细菌和病毒感染。疟疾感染红细胞，导致红细胞破裂，释放寄生虫和寄生虫副产品。血红素是红细胞血红蛋白的分解产物。血红素被一种酶（血红素加氧酶-1; HO-1）降解，产生可以改变免疫反应的分子，并可能解释疟疾感染期间观察到的免疫调节作用。这项研究的目的是确定HO-1是否改变了对疟疾和伴随细菌感染的免疫反应。这将在实验感染的小鼠和自然获得性疟疾感染的人中进行检查。感染的结果是否可以通过改变HO-1的活性来改变将被评估。已经有药物可用于人类上调或下调HO-1。如果改变HO-1活性具有有益效果，这些药物可以很容易地用于疟疾。这项研究将在英国和冈比亚进行，那里每年有成千上万的儿童受到疟疾的严重影响。

Malaria is a tropical disease that kills in its own right and weakens immune defences against other infections. Malaria-infected children are less responsive to vaccination and more susceptible to bacterial and viral infections. Malaria infects red blood cells, causing them to burst, releasing parasites and parasite by-products. Heme is a breakdown product of red blood cell haemoglobin. Heme is degraded by an enzyme (heme oxygenase-1; HO-1) to produce molecules that can modify immune responses, and may account for the immunomodulation seen during malaria infection.The aim of the research is to determine whether HO-1 modifies the immune response to malaria and to concomitant bacterial infections. This will be examined in experimentally-infected mice and in people with naturally-acquired malaria infections. Whether the outcome of infections can be modified by changing the activity of HO-1 will be assessed.Drugs are already available for use in humans to either up- or down-regulate HO-1. These drugs could easily be used in malaria if altering HO-1 activity had beneficial effects. This research will be carried out in the UK and in The Gambia, where many thousands of children are severely affected by malaria every year.