<i>Trypanosoma evansi</i> evades host innate immunity by releasing extracellular vesicles to activate TLR2-AKT signaling pathway

Surra, one of the most important animal diseases with economic consequences in Asia and South America, is caused by <i>Trypanosoma evansi</i>. However, the mechanism of immune evasion by <i>T. evansi</i> has not been extensively studied. In the present study, <i>T. evansi</i> extracellular vesicles (TeEVs) were characterized and the role of TeEVs in <i>T. evansi</i> infection were examined. The results showed that <i>T. evansi</i> and TeEVs could activate TLR2-AKT pathway to inhibit the secretions of IL-12p40, IL-6, and TNF-α in mouse BMDMs. TLR2^−/- mice and mice with a blocked AKT pathway were more resistant to <i>T. evansi</i> infection than wild type (WT) mice, with a significantly lower infection rate, longer survival time and less parasite load, as well as an increased secretion level of IL-12p40 and IFN-γ. Kinetoplastid membrane protein-11 (KMP-11) of TeEVs could activate AKT pathway and inhibit the productions of IL-12p40, TNF-α, and IL-6 <i>in vitro</i>. TeEVs and KMP-11 could inhibit the productions of IL-12p40 and IFN-γ, promote <i>T. evansi</i> proliferation and shorten the survival time of infected mice <i>in vivo</i>. In conclusion, <i>T. evansi</i> could escape host immune response through inhibiting the productions of inflammatory cytokines via secreting TeEVs to activate TLR2-AKT pathway. KMP-11 in TeEVs was involved in promoting <i>T. evansi</i> infection. Extracellular vesicles (EVs) secreted by <i>Trypanosoma evansi</i> (<i>T. evansi</i>) activate the TLR2-AKT signaling pathway to inhibit the production of inflammatory cytokines, thereby escaping the host’s immune response. Kinetoplastid membrane protein-11 (KMP-11) in EVs is related to the promotion of <i>T.</i> infection via AKT pathway.苏拉病（Surra）是在亚洲与南美洲极具经济影响力的重要动物疫病之一，其病原体为伊氏锥虫（Trypanosoma evansi）。然而，目前针对伊氏锥虫免疫逃逸机制的研究尚不够广泛。本研究对伊氏锥虫胞外囊泡（TeEVs）进行了系统表征，并探究了其在伊氏锥虫感染过程中的作用。研究结果显示，伊氏锥虫及其胞外囊泡可激活TLR2-AKT通路，抑制小鼠骨髓源性巨噬细胞（BMDMs）中IL-12p40、IL-6与TNF-α的分泌。TLR2基因敲除（TLR2⁻/⁻）小鼠与AKT通路阻断小鼠相较于野生型（WT）小鼠，对伊氏锥虫感染的抗性显著提升，表现为感染率降低、存活时间延长、寄生虫载量减少，同时IL-12p40与IFN-γ的分泌水平升高。胞外囊泡中的动质体膜蛋白-11（Kinetoplastid membrane protein-11, KMP-11）可在体外激活AKT通路，并抑制IL-12p40、TNF-α及IL-6的产生。胞外囊泡与KMP-11可在体内抑制IL-12p40与IFN-γ的产生，促进伊氏锥虫增殖并缩短感染小鼠的存活时间。综上，伊氏锥虫可通过分泌胞外囊泡激活TLR2-AKT通路，抑制炎性细胞因子的产生，从而逃逸宿主的免疫应答。胞外囊泡中的KMP-11通过AKT通路参与促进伊氏锥虫感染。伊氏锥虫分泌的胞外囊泡（EVs）可激活TLR2-AKT信号通路，抑制炎性细胞因子的产生，进而逃逸宿主免疫应答。胞外囊泡中的动质体膜蛋白-11（KMP-11）可通过AKT通路参与促进伊氏锥虫感染。