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.1007298Posted by Dr. Tim Sandle, Pharmaceutical Microbiology
