P2X7 receptor drives Th1 cell differentiation and controls the follicular helper T cell population to protect against Plasmodium chabaudi malaria

摘要: A complete understanding of the mechanisms underlying acquisition protective immunity is crucial to improve vaccine strategies eradicate malaria. However, it still unclear whether recognition damage signals influences immune response Plasmodium infection. Adenosine triphosphate (ATP) accumulates in infected erythrocytes and released into extracellular milieu through ion channels erythrocyte membrane or upon rupture. The P2X7 receptor senses ATP induces CD4 T cell activation death. Here we show that promotes helper 1 (Th1) differentiation detriment follicular (Tfh) cells during blood-stage chabaudi was activated following rupture these became highly responsive acute Moreover, mice lacking had increased susceptibility infection, which correlated with impaired Th1 differentiation. Accordingly, IL-2 IFNγ secretion, as well T-bet expression, critically depended on signaling cells. Additionally, controlled splenic Tfh population by promoting apoptotic-like Finally, required generate a balanced Th1/Tfh an improved ability transfer parasite protection CD4-deficient mice. This study provides new insight malaria immunology showing importance controlling fine-tuning between P. infection thus disease outcome.