Elimination of Hepatic Rodent Plasmodium Parasites by Amino Acid Supplementation

Abstract

Summary Plasmodium 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.

Avian Malaria Parasites Modulate Gut Microbiome Assembly in Canaries

“…Beyond changes in taxonomic profiles, the metabolites produced by specific bacterial species in the gut exert systemic effects on the host [ 72 ], as well as influence malaria infection and disease severity [ 73 ]. According to our study, most of the unique pathways identified in the microbiome of Plasmodium -infected birds could not be directly associated with avian malaria infection, however a PWY5F9-12 (biphenyl degradation) and PWY-3081 (L-lysine biosynthesis V) could be involved in anti-malarial response [ 74 , 75 ]. The presence of pathways of toluene degradation in the Plasmodium -infected birds could also be as response to the infection due to the production of toluene by the parasite [ 76 , 77 ].…”

Amino Acid Metabolism in Apicomplexan Parasites

“…In vivo studies in mice showed that supplementation of a cocktail of amino acids (arginine, lysine, and valine (RKV)) during the liver stage of Plasmodium parasites abolished proliferation, as the amino acids played a crucial role in boosting the innate immune response. RKV activated MyD88, a crucial adaptor molecule involved in Toll-like receptor (TLR)-mediated signal transduction, essential for the function of myeloid cells and subsequent parasite elimination [67].…”

“…In the hepatic stage of Plasmodium spp., where parasites cannot rely on hemoglobin degradation to obtain their amino acids, normal development of P. berghei was largely dependent on the arginine transporter PbNPT1 [26]. Separately, in a more recent in vivo study, dietary supplementation of mice with a combination of arginine (R) and two additional amino acids, lysine (K) and valine (V), termed RKV, significantly decreased Plasmodium late liver-stage infection [67]. It was shown that exogenously supplied RKV stimulates the host's overall innate immune response, suggesting that amino acids, apart from their metabolic roles for cell survival, can also act as activators of downstream inflammatory signaling pathways and can be exploited for intervention against a specific lifecycle stage [67].…”

Prophylaxis of malaria by Artemisia infusions: The key role of lysine

“…A recent paper from Portugal has studied the role of amino acids in depth and comes to very convincing conclusions. 7 We extract one figure from their paper. Drinking an aqueous solution of argininelysine-valine (RKV) several weeks before the infection significantly reduces the liver infection load (Figure 1).…”