2018-10-17| Asia-Pacific

Singapore researcher’s breakthrough offers fresh hopes of combating malaria

by Rajaneesh K. Gopinath
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By Rajaneesh K. Gopinath, Ph.D.

A research collaboration between scientists from MIT, Singapore-MIT Alliance for Research and Technology (SMART) and Nanyang Technological University has resulted in the discovery of a new pathway that holds potential therapeutic value.

Malaria is a parasitic disease that is preventable and curable. Yet, in 2016, the World Health Organization (WHO), reported of an estimate of 216 million cases of malaria in 91 countries, which is an increase of 5 million cases from the previous year. Activated Natural killer (NK) cells present in our body acts as a first line of defense against the infection. NK cells can recognize pathogens by pattern-recognition receptors (PRR) and directly lyses the Plasmodium-infected red blood cells (iRBCs) via cell-mediated cytotoxicity. However, it is commonly observed that the NK cell response to infection varies between populations. The detailed molecular mechanisms explaining why NK cells in certain people gets activated effectively while it does not in some others, have largely eluded the scientific community.

After deeply analyzing responsive and non-responsive NK cells, a group of researchers from Singapore have finally shed light on this mystery. A novel molecular pathway by which NK cells detect iRBCs has been discovered. The team found that NK cells differentially expressed MDA5, a RIG-I-like receptor involved in sensing cytosolic RNAs. The receptor recognizes small RNA containing microvesicles secreted by iRBCs which triggers the NK cells into attacking them. The higher the MDA-5 expression, the better the NK cells respond to infection. Once this connection was made, the researchers proceeded to test whether non-responsive NK cells could be activated by manipulating their MDA5 levels. By using a small molecule agonist, they indeed succeeded in improving non-responder NK cells to clear iRBC. The authors believe this could prove to an effective therapeutic strategy towards combating malaria in the future. The results of this study are published in PLOS Pathogens.





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