Supplement of L-Arg improves protective immunity during early-stage Plasmodium yoelii 17XL infection

被引:18
作者
Zhu, X. [1 ,2 ]
Pan, Y. [1 ]
Li, Y. [1 ]
Cui, L. [3 ]
Cao, Y. [1 ]
机构
[1] China Med Univ, Coll Basic Med Sci, Dept Immunol, Shenyang 110001, Liaoning, Peoples R China
[2] China Med Univ, Inst Pathol & Pathophysiol, Shenyang 110001, Liaoning, Peoples R China
[3] Penn State Univ, Dept Entomol, University Pk, PA 16802 USA
基金
中国国家自然科学基金;
关键词
activation; arginine; dendritic cell; immune response; Plasmodium yoelii; rodent malaria;
D O I
10.1111/j.1365-3024.2012.01374.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-?+ T cells and F4/80+CD36+ macrophages during early-stage infection, which were accompanied by enhanced synthesis of IFN-?, TNF-a 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.
引用
收藏
页码:412 / 420
页数:9
相关论文
共 52 条
[1]  
(2010)
[2]  
John C.C., Kutamba E., Mugarura K., Opoka R.O., Adjunctive therapy for cerebral malaria and other severe forms of Plasmodium falciparum malaria, Expert Rev Anti Infect Ther, 8, pp. 997-1008, (2010)
[3]  
Weinberg J.B., Lopansri B.K., Mwaikambo E., Granger D.L., Arginine, nitric oxide, carbon monoxide, and endothelial function in severe malaria, Curr Opin Infect Dis, 21, pp. 468-475, (2008)
[4]  
Omodeo-Sale F., Cortelezzi L., Vommaro Z., Scaccabarozzi D., Dondorp A.M., Dysregulation of L-arginine metabolism and bioavailability associated to free plasma heme, Am J Physiol Cell Physiol, 299, (2010)
[5]  
Boger R.H., Bode-Boger S.M., The clinical pharmacology of L-arginine, Annu Rev Pharmacol Toxicol, 41, pp. 79-99, (2001)
[6]  
Yeo T.W., Lampah D.A., Gitawati R., Et al., Impaired nitric oxide bioavailability and L-arginine-reversible endothelial dysfunction in adults with falciparum malaria, J Exp Med, 204, pp. 2693-2704, (2007)
[7]  
Yeo T.W., Lampah D.A., Gitawati R., Et al., Safety profile of L-arginine infusion in moderately severe falciparum malaria, PLoS One, 3, (2008)
[8]  
Peranzoni E., Marigo I., Dolcetti L., Et al., Role of arginine metabolism in immunity and immunopathology, Immunobiology, 212, pp. 795-812, (2007)
[9]  
Malhotra I., Mungai P., Muchiri E., Et al., Distinct Th1- and Th2-Type prenatal cytokine responses to Plasmodium falciparum erythrocyte invasion ligands, Infect Immun, 73, pp. 3462-3470, (2005)
[10]  
Taylor-Robinson A.W., Phillips R.S., Severn A., Moncada S., Liew F.Y., The role of TH1 and TH2 cells in a rodent malaria infection, Science, 260, pp. 1931-1934, (1993)