Malaria-infected red blood cells trigger the immune system's first line of defense by releasing small vesicles that activate a pathogen recognition receptor called MDA5, according to a study published October 4 in the open-access journal PLOS Pathogens by Peter Preiser of Nanyang Technological University in Singapore and Jianzhu Chen of the Massachusetts Institute of Technology, and colleagues.
Malaria is a major public health concern caused by parasitic microorganisms that belong to the genus Plasmodium. A better understanding of early host response and the determinants of immunity are essential to developing innovative therapeutic approaches. Natural killer cells are important immune cells that provide the first line of defense against malaria infection but show significant differences in their responses in the human population. The molecular mechanisms through which natural killer cells are activated by parasites are largely unknown, and so is the molecular basis underlying the variation in natural killer cell responses to malaria infection in the human population. To address this gap in knowledge, Preiser, Chen and colleagues analyzed transcriptional differences between human natural killer cells that respond and don't respond to malaria infection.
Natural killer cells that responded to Plasmodium-infected red blood cells had higher levels of MDA5, which was activated by small vesicles released from the infected cells. Treatment with a small molecule that activated MAD5 restored the ability of non-responder natural killer cells to clear infected red blood cells. The findings suggest that MDA5 could contribute to variation in natural killer cell responses to malaria infection in the human population. Moreover, the study provides new insights into a mechanism by which natural killer cells are activated by parasites and reveals a possible molecular target to control malaria infection in humans.
"The study reveals how natural killer cells recognize parasite-infected red blood cells and possible approaches to treat malaria infection by boosting host immunity," says corresponding author Jianzhu Chen.
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PLOS Pathogens