Key to cure bloodstream malaria infections identified
London: Researchers have discovered how malaria manipulates the immune system to allow the parasite to persist in the bloodstream.
By rescuing this immune system pathway, University of Iowa researchers and colleagues were able to cure mice of bloodstream malaria infections.
The findings could point the way to a new approach for treating malaria that does not rely on vaccination and is not susceptible to the parasite’s notorious ability to develop drug resistance.
“Malaria is chronic, prolonged infection and the host immune defense has a tough time clearing it and sometimes it never clears it,” said Noah Butler, Ph.D., UI postdoctoral research scholar and lead study author.
“We’ve determined that this prolonged infection actually drives dysfunction of the immune cells that are supposed to be fighting the infection, which in essence allows further persistence of the parasite infection,” Butler explained.
More specifically, the study showed that the malaria parasite stimulate these key immune cells (known as CD4+ T cells) so that they continuously express molecules called inhibitory receptors.
Under normal circumstances, these molecules help to “apply the brakes” to the immune response and prevent over-activation that can be harmful.
However, by keeping the mechanism turned on, the malaria parasite damps down the immune response significantly, reducing the T cells’ ability to fight the parasite and allowing it to persist.
Importantly, the team also showed that blocking the action of the inhibitory receptor molecules resulted in immediate and complete clearance of the malaria parasite.
“When we blocked the function of these molecules, we took the brakes off the host’s immune response and everything got better - the overall immune response was dramatically improved and there was immediate control and accelerated clearance of the parasite,” noted John Harty, PhD, professor of microbiology and pathology at the UI Carver College of Medicine and senior study author.
“These findings suggest an alternative approach for the treatment of existing malaria infection,” he concluded.
Harty noted that the current study was done in mice and it is not yet known if the same approach will work in humans.
The findings were published December 11 in the Advance Online Publication of the journal Nature Immunology.