ABSTRACT

Surra, one of the most important animal diseases with economic consequences in Asia and South America, is caused by Trypanosoma evansi. However, the mechanism of immune evasion by T. evansi has not been extensively studied. In the present study, T. evansi extracellular vesicles (TeEVs) were characterized and the role of TeEVs in T. evansi infection were examined. The results showed that T. evansi 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 T. evansi 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 in vitro. TeEVs and KMP-11 could inhibit the productions of IL-12p40 and IFN-γ, promote T. evansi proliferation and shorten the survival time of infected mice in vivo. In conclusion, T. evansi 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 T. evansi infection.

Extracellular vesicles (EVs) secreted by Trypanosoma evansi (T. evansi) 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 T.evansi infection via AKT pathway.

摘要

Surra 是在亚洲和南美洲具有经济影响的最重要的动物疾病之一，是由埃文氏锥虫引起的。然而，T. evansi的免疫逃避机制尚未得到广泛研究。在本研究中，T. evansi细胞外囊泡 (TeEVs) 进行了表征，并检查了 TeEVs 在T. evansi感染中的作用。结果表明，T. evansi和 TeEVs 可以激活 TLR2-AKT 通路，抑制小鼠 BMDMs 中 IL-12p40、IL-6 和 TNF-α 的分泌。TLR2 ^-/-小鼠和 AKT 通路受阻的小鼠对埃文西丝虫更具抵抗力与野生型（WT）小鼠相比，感染率显着降低，存活时间更长，寄生虫负荷更少，IL-12p40和IFN-γ的分泌水平增加。TeEVs 的动质体膜蛋白 11 (KMP-11) 可在体外激活 AKT 通路并抑制 IL-12p40、TNF-α 和 IL-6的产生。TeEVs 和 KMP-11 可以抑制 IL-12p40 和 IFN-γ 的产生，促进T. evansi增殖并缩短感染小鼠的体内存活时间。综上所述，埃文西氏菌可以通过分泌TeEVs来激活 TLR2-AKT 通路来抑制炎症细胞因子的产生，从而逃避宿主免疫反应。TeEVs 中的 KMP-11 参与了推广T. evansi感染。

伊氏锥虫( T. evansi ) 分泌的细胞外囊泡 ( EVs ) 激活 TLR2-AKT 信号通路，抑制炎性细胞因子的产生，从而逃避宿主的免疫反应。EV 中的动质体膜蛋白 11 (KMP-11) 与通过 AKT 途径促进T.evansi感染有关。