Department of Biochemistry and Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Parasite Immunol. 2012 Jul;34(7):372-82. doi: 10.1111/j.1365-3024.2012.01367.x.
Studies have shown that glycosylphosphatidylinositols (GPIs) of Plasmodium falciparum activate macrophages mainly through Toll-like receptor 2 (TLR2)-mediated signalling and to certain extent through TLR4-mediated signalling to induce proinflammatory cytokine production. However, the ability of parasite GPIs to activate dendritic cells (DCs) has not been reported. Here, we show that parasite GPIs efficiently activate DCs through TLR2-mediated signalling mechanism and induce the production of TNF-α and IL-12. We also studied the role of scavenger receptor CD36 in P. falciparum GPI- and merozoite-induced cytokine responses by DCs. The results indicate that CD36 modulates the cytokine-inducing activity of the parasite GPIs by collaborating with TLR2 in DCs. Furthermore, our data reveal that CD36 modulates the activity of P. falciparum merozoites, likely by the contribution of phagocytosis-coupled CD36-mediated signalling to the signalling induced by merozoites. Altogether, these results contribute towards understanding of signalling mechanisms in malaria parasite-induced activation of the innate immune system.
研究表明疟原虫的糖基磷脂酰肌醇（GPI）通过 Toll 样受体 2（TLR2）介导的信号通路，在一定程度上通过 TLR4 介导的信号通路激活巨噬细胞，诱导前炎性细胞因子的产生。然而，寄生虫 GPI 激活树突状细胞（DC）的能力尚未见报道。在这里，我们发现寄生虫 GPI 通过 TLR2 介导的信号机制有效地激活 DC，并诱导 TNF-α和 IL-12 的产生。我们还研究了清道夫受体 CD36 在疟原虫 GPI 和裂殖子诱导的 DC 细胞因子反应中的作用。结果表明，CD36 通过与 DC 中的 TLR2 合作，调节寄生虫 GPI 诱导细胞因子的活性。此外，我们的数据揭示了 CD36 调节疟原虫裂殖子的活性，可能是通过吞噬作用偶联的 CD36 介导的信号通路对裂殖子诱导的信号通路的贡献。总之，这些结果有助于理解疟原虫诱导的先天免疫系统激活中的信号机制。
