<p>In malaria-endemic regions, asymptomatic <i>Plasmodium falciparum</i> infections during periods of low transmission alternate with symptomatic infections during periods of high transmission. The mechanisms underlying <i>P. falciparum</i> persistence without causing symptoms during low-transmission periods remain unclear. Here we analysed the plasma metabolome (<i>n</i> = 199) of individuals in the Gambia, West Africa, during the high and low malaria transmission periods. We observed significant metabolome changes associated with seasonality and to a lesser extent with malaria pathogenicity. We show that plasma levels of taurine, an amino sulfonic acid, increase longitudinally during periods of low transmission. Although taurine showed no effect on the development of cultured parasites in vitro, it strongly inhibited and prevented malaria-infected red blood cell (iRBC) adhesion via PfEMP1 to the common adhesion receptor CD36 and the endothelial protein C receptor, which is linked to cerebral malaria. We reveal a role for taurine in reducing cytoadhesion, which could inform strategies to reduce symptomatic malaria in sub-Saharan Africa.</p>

错误:搜索内容不能为空,请输入英文关键词
错误:关键词超出字数限制,请精简
高级检索

Longitudinal plasma metabolomics reveals a role for taurine in asymptomatic malaria and seasonal persistence

  • Gretchen Diffendall,
  • Perine Millot,
  • Patty Chen,
  • Balotin Fogang,
  • Dominique Dorin-Semblat,
  • Fanny Aprahamian,
  • Sylvère Durand,
  • Benoît Gamain,
  • Antoine Claessens,
  • Artur Scherf

摘要

In malaria-endemic regions, asymptomatic Plasmodium falciparum infections during periods of low transmission alternate with symptomatic infections during periods of high transmission. The mechanisms underlying P. falciparum persistence without causing symptoms during low-transmission periods remain unclear. Here we analysed the plasma metabolome (n = 199) of individuals in the Gambia, West Africa, during the high and low malaria transmission periods. We observed significant metabolome changes associated with seasonality and to a lesser extent with malaria pathogenicity. We show that plasma levels of taurine, an amino sulfonic acid, increase longitudinally during periods of low transmission. Although taurine showed no effect on the development of cultured parasites in vitro, it strongly inhibited and prevented malaria-infected red blood cell (iRBC) adhesion via PfEMP1 to the common adhesion receptor CD36 and the endothelial protein C receptor, which is linked to cerebral malaria. We reveal a role for taurine in reducing cytoadhesion, which could inform strategies to reduce symptomatic malaria in sub-Saharan Africa.