Blessing In Disguise
Sickle-cell may blunt malaria
People who carry one copy of a mutation that leads to sickle-cell disease are protected from the worst effects of malaria, research shows. A sickled red blood cell is shown (top) alongside normal red blood cells)
Sickle-cell hemoglobin may gas malaria into submission, a new study proposes. People who carry a mutation that deforms the oxygen-carrying protein in red blood cells are well-known to be protected against malaria. Scientists used to think the mutation prevented the malaria parasite from getting into blood cells. But researchers led by Miguel Soares at the Instituto Gulbenkian de Ciência in Oeiras, Portugal, now suggest another mechanism. The sickle-cell mutation leads to higher production of a protein called heme oxygenase-1, which makes carbon monoxide gas. The gas helps reduce inflammation and protects against death in mice with malaria infection in their brains, the team reports in the April 29 Cell. Using mice genetically engineered to make human hemoglobin with the sickle-cell mutation, Soares and his colleagues discovered that the mutation primes the body to deal with the red blood cellshredding activities of the malaria parasite. Hemoglobin breaks down more easily in people with the sickle mutation, Soares says, releasing a toxic compound called heme. To compensate, the body makes more of the heme oxygenase-1 enzyme, leading to more carbon monoxide production. The carbon monoxide then latches on to hemoglobin and prevents heme from popping off and causing more trouble. "Before you get infected, sickle hemoglobin is releasing tiny amounts of heme. Your body looks at it and says, 'This could be very dangerous, so I'm going to shut it down,'" Soares says. Priming the body to deal with the extra heme also means that cells are prepared for the effects of the malaria parasite. The parasite can still infect cells, but the host doesn't get as sick, allowing more time for the immune system to deal with the infection. "It's a politician's approach; you open a dialog with it while you're still fighting it."
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