Abstract
SummaryPlasmodium parasites, causative agents of malaria, scavenge host nutrients to sustain their intracellular replication. Modulation of the host's nutritional status can potentially help control infection by limiting the parasite's access to nutrients, or by boosting the immune system. Here, we show that dietary supplementation of mice employing a combination of arginine (R) with two additional amino acids, lysine (K) and valine (V), termed RKV, significantly decreases Plasmodium liver infection. RKV supplementation results in the elimination of parasites at a late stage of their development in the liver. Our data employing genetic knockout mouse models and in vivo depletion of specific cell populations suggest that RKV supplementation boosts the host's overall innate immune response, and that parasite elimination is dependent on MyD88 signaling in immune cells. The immunostimulatory effect of RKV supplementation opens a potential role for dietary supplementation as an adjuvant for prophylaxis or immunization strategies against Plasmodium infection.
Highlights
Malaria is an infectious disease that remains a major cause of morbidity and mortality worldwide, for which new cost-effective interventions are urgently needed (WHO, 2019)
We show that dietary supplementation of mice employing a combination of arginine (R) with two additional amino acids, lysine (K) and valine (V), termed RKV, significantly decreases Plasmodium liver infection
RKV Dietary Supplementation Impairs P. berghei Hepatic Infection To assess the possibility of modulating hepatic infection by Plasmodium through dietary supplementation, we sought to increase the bioavailabilty of Arg (R) as a physiological substrate for the synthesis of nitric oxide (NO), which is a key mediator of immune responses (Lee et al, 2017; Roth, 1992; Bogdan, 2001)
Summary
Malaria is an infectious disease that remains a major cause of morbidity and mortality worldwide, for which new cost-effective interventions are urgently needed (WHO, 2019). The end of the liver stage of Plasmodium infection is marked by the release of these newly formed parasites into the bloodstream, where they invade red blood cells, and initiate the symptomatic, erythrocytic stage of the disease (Prudencio et al, 2006). Dietary supplementations employing various nutrients, such as Coenzyme Q10, Vitamin C, Vitamin D, iron, Arg, tetrahydrobiopterin (BH4), or folate, among others, have been shown to directly impact Plasmodium erythrocytic stages (Nyariki et al, 2019; Qin et al, 2019; Wu et al, 2018; Castberg et al, 2018; Goheen et al, 2017; Awasthi et al, 2017; Alkaitis and Ackerman, 2016; Meadows et al, 2015). Despite numerous studies to understand how different nutrients may affect Plasmodium infection, their usefulness as modulators of disease remains largely unexplored
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
