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

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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.