How malaria infection activates natural killer cells

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.

See:

Weijian Ye, Marvin Chew, Jue Hou, Fritz Lai, Stije J. Leopold, Hooi Linn Loo, Aniruddha Ghose, Ashok K. Dutta, Qingfeng Chen, Eng Eong Ooi, Nicholas J. White, Arjen M. Dondorp, Peter Preiser, Jianzhu Chen. Microvesicles from malaria-infected red blood cells activate natural killer cells via MDA5 pathway. PLOS Pathogens, 2018; 14 (10): e1007298 DOI: 10.1371/journal.ppat.1007298

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology