PMID- 34348595 OWN - NLM STAT- MEDLINE DCOM- 20220127 LR - 20220127 IS - 2150-5608 (Electronic) IS - 2150-5594 (Print) IS - 2150-5594 (Linking) VI - 12 IP - 1 DP - 2021 Dec TI - Trypanosoma evansi evades host innate immunity by releasing extracellular vesicles to activate TLR2-AKT signaling pathway. PG - 2017-2036 LID - 10.1080/21505594.2021.1959495 [doi] AB - 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-alpha 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-gamma. Kinetoplastid membrane protein-11 (KMP-11) of TeEVs could activate AKT pathway and inhibit the productions of IL-12p40, TNF-alpha, and IL-6 in vitro. TeEVs and KMP-11 could inhibit the productions of IL-12p40 and IFN-gamma, 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. FAU - Wei, Ran AU - Wei R AD - Key Laboratory of Zoonosis Research, Ministry of Education; College of Veterinary Medicine, Jilin University, Changchun, China. FAU - Li, Xin AU - Li X AD - Key Laboratory of Zoonosis Research, Ministry of Education; College of Veterinary Medicine, Jilin University, Changchun, China. FAU - Wang, Xiaocen AU - Wang X AD - Key Laboratory of Zoonosis Research, Ministry of Education; College of Veterinary Medicine, Jilin University, Changchun, China. FAU - Zhang, Nan AU - Zhang N AD - Key Laboratory of Zoonosis Research, Ministry of Education; College of Veterinary Medicine, Jilin University, Changchun, China. FAU - Wang, Yuru AU - Wang Y AD - Key Laboratory of Zoonosis Research, Ministry of Education; College of Veterinary Medicine, Jilin University, Changchun, China. FAU - Zhang, Xichen AU - Zhang X AD - Key Laboratory of Zoonosis Research, Ministry of Education; College of Veterinary Medicine, Jilin University, Changchun, China. FAU - Gong, Pengtao AU - Gong P AD - Key Laboratory of Zoonosis Research, Ministry of Education; College of Veterinary Medicine, Jilin University, Changchun, China. FAU - Li, Jianhua AU - Li J AD - Key Laboratory of Zoonosis Research, Ministry of Education; College of Veterinary Medicine, Jilin University, Changchun, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Virulence JT - Virulence JID - 101531386 RN - 0 (Cytokines) RN - 0 (Interleukin-12 Subunit p40) RN - 0 (Interleukin-6) RN - 0 (Protozoan Proteins) RN - 0 (Tlr2 protein, mouse) RN - 0 (Toll-Like Receptor 2) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Cytokines MH - *Extracellular Vesicles MH - *Immune Evasion MH - *Immunity, Innate MH - Interleukin-12 Subunit p40 MH - Interleukin-6 MH - Mice MH - Mice, Knockout MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Protozoan Proteins/immunology MH - Signal Transduction MH - Toll-Like Receptor 2/*metabolism MH - *Trypanosoma/immunology/pathogenicity MH - Tumor Necrosis Factor-alpha PMC - PMC8344757 OTO - NOTNLM OT - AKT OT - KMP-11 OT - TLR2 OT - Trypanosoma evansi OT - extracellular vesicles OT - immune evasion COIS- The authors declare that they have no competing interests. EDAT- 2021/08/06 06:00 MHDA- 2022/01/28 06:00 PMCR- 2021/08/05 CRDT- 2021/08/05 05:29 PHST- 2021/08/05 05:29 [entrez] PHST- 2021/08/06 06:00 [pubmed] PHST- 2022/01/28 06:00 [medline] PHST- 2021/08/05 00:00 [pmc-release] AID - 1959495 [pii] AID - 10.1080/21505594.2021.1959495 [doi] PST - ppublish SO - Virulence. 2021 Dec;12(1):2017-2036. doi: 10.1080/21505594.2021.1959495.