Taha Ali

Pyruvate and Glutamine Significantly Reduce Parasite Burden in Experimental Malaria Trials

Abstract

The worldwide malaria epidemic remains one of the worst global health crises in the world currently with 225 million cases and 1 million deaths yearly. Individuals infected by the malaria mosquitoes are susceptible to repeated infections and only then will the body develop an immunity to the symptoms through the work of high-quality germinal B cells (GC B cells). Researchers have tried to find solutions to this epidemic by developing malaria vaccines, drugs, and insecticide-resistant mosquito vectors. All of these are yet to develop as effective treatment options. The focus has now shifted to developing long-lasting antibody-mediated immunity to malaria. Here, we propose the use of glutamine and pyruvate as stimulators for the tricarboxylic acid (TCA) cycle to produce more high-affinity memory B cells (MBCs) and long-lived plasma cells (LLPCs) to fight off malaria parasites. We used genetically engineered P. yoelii infected mice and treatments of pyruvate, glutamine, and a combination of both metabolites to test their ability to reduce malaria infection. The results suggest that pyruvate significantly reduces parasite burden in mice even though glutamine and pyruvate produce approximately the same number of T follicular helper cells and GC B cells. This study supports the rationale to further investigate pyruvate supplementation as a therapeutic modality to boost the metabolism of GC B cells and secrete protective antibodies. Metabolite supplementation may have the potential to overcome immune failures during Plasmodium infection and serve as a clinically relevant strategy for individuals in malaria-endemic areas.