Supplement of L-Arg improves protective immunity during early-stage Plasmodium yoelii 17XL infection.
L-arginine (L-Arg), the precursor of nitric oxide (NO), plays multiple important roles in nutrient metabolism and immune regulation. L-Arg supplement serves as a potential adjunctive therapy for severe malaria, because it improves NO bioavailability and reverses endothelial dysfunction in severe malaria patients. In this study, we investigated the effect of dietary L-Arg supplement on host immune responses during subsequent malaria infection using the Plasmodium yoelii 17XL - BALB/c mouse model. We have shown that pretreatment of mice with L-Arg significantly decreased parasitemia and prolonged the survival time of mice after infection. L-Arg supplement led to significant increases in activated CD4(+)T-bet(+)IFN-γ(+) T cells and F4/80(+)CD36(+) macrophages during early-stage infection, which were accompanied by enhanced synthesis of IFN-γ, TNF-α and NO by spleen cells. Moreover, L-Arg-pretreated mice developed more splenic myeloid and plasmacytoid dendritic cells with up-regulated expression of MHC II, CD86 and TLR9. In comparison, L-Arg treatment did not change the number of regulatory T cells and the level of anti-inflammatory cytokine IL-10. Taken together, our results showed that L-Arg pretreatment could improve the protective immune response in experimental malaria infection in mice, which underlines potential importance of L-Arg supplement in malaria-endemic human populations.
Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China.
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Zhu
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Pan
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Li
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Cui
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Cao
D000818:Animals; D001120:Arginine / Q000008:administration & dosage*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004032:Diet / Q000379:methods*; D019587:Dietary Supplements; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D008288:Malaria / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D018512:Parasitemia / Q000517:prevention & control; D010967:Plasmodium yoelii / Q000276:immunology* / Q000472:pathogenicity*; D016019:Survival Analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology
D007371:Interferon-gamma; D001120:Arginine