Researchers at Duke University Medical Center might have discovered why people with sickle cell disease get milder cases of malaria than individuals who have normal red blood cells. The findings appear in the journal Cell Host and Microbe.

In a finding that has eluded scientists for years, Duke researchers discovered that genetic material in red blood cells might help alter parasite activity via a novel mechanism that alters parasite gene regulation.

"One of the most interesting findings in our study is that the human microRNA found in sickle red cells directly participate in the gene regulation of malaria parasites," said Jen-Tsan Chi, MD, PhD, senior author and associate professor in the Duke Institute for Genome Sciences and Policy and Department of Molecular Genetics and Microbiology. "These microRNAs enriched in the sickle red cells reduce the parasite’s ability to propagate, so that certain people stay more protected."

MicroRNAs are small units of RNA, which come from DNA. MicroRNAs are only 20-25 nucleotides long and help to regulate gene expression.

The scientists also showed that when two different microRNAs were introduced at higher levels in normal red cells, the parasite growth also was decreased.

The malaria parasites grow in the human red cells, cells that scientists thought lacked any genetic material. Many scientists had looked for the components in sickle cells that could help them resist the parasite, but the Duke researchers found one component by thinking outside of scientific norms.

The Duke team found microRNAs in the red blood cells and showed that their composition is dramatically different in the sickle red blood cells. Counter to what they expected, they showed that these differences directly contribute to the malaria resistance in sickle cell disease.

The scientists also conducted a different experiment that showed blocking these microRNAs (miR-451 and Let-7i is particular) in sickle cells reduced the ability of the cells to protect against malaria.

"If you block the miRNAs, the parasite grows two or three times as well," Chi said.

Another surprise in this investigation was the presence of a chimera, a fusion of human microRNA with the parasites’ mRNAs.