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

References

• Aregawi WG, Agga GE, Abdi RD, et al. Systematic review and meta-analysis on the global distribution, host range, and prevalence of Trypanosoma evansi. Parasit Vectors. 2019;12:67.
   PubMed Web of Science ®Google Scholar
• Birhanu H, Roge S, Simon T, et al. Surra Sero K-SeT, a new immunochromatographic test for serodiagnosis of Trypanosoma evansi infection in domestic animals. Vet Parasitol. 2015;211(3–4):153–157.
   PubMed Web of Science ®Google Scholar
• Desquesnes M, Dargantes A, Lai D-H, et al. Trypanosoma evansi and Surra: a review and perspectives on transmission, epidemiology and control, impact, and zoonotic aspects. Biomed Res Int. 2013;2013:20.
   Web of Science ®Google Scholar
• Elhaig MM, Sallam NH. Molecular survey and characterization of Trypanosoma evansi in naturally infected camels with suspicion of a Trypanozoon infection in horses by molecular detection in Egypt. Microb Pathog. 2018;123:201–205.
   PubMed Web of Science ®Google Scholar
• Rashid I, Akbar H, Gharbi M, et al. First report of Trypanosoma Evansi Infection (SURRA) IN A PUMA (FELIS CONCOLOR) OF LAHORE ZOO, PAKISTAN. J Zoo Wildl Med. 2017;48(3):918–921.
   PubMed Web of Science ®Google Scholar
• Herrera HM, Norek A, Freitas TP, et al. Domestic and wild mammals infection by Trypanosoma evansi in a pristine area of the Brazilian Pantanal region. Parasitol Res. 2005;96:121–126.
   PubMed Web of Science ®Google Scholar
• Ereqat S, Nasereddin A, Al-Jawabreh A, et al. Prevalence of Trypanosoma evansi in livestock in Palestine. Parasit Vectors. 2020;13:21.
   PubMed Web of Science ®Google Scholar
• Van Vinh Chau N, Buu Chau L, Desquesnes M, et al. A clinical and epidemiological investigation of the first reported human infection with the zoonotic parasite Trypanosoma evansi in Southeast Asia. Clin Infect Dis. 2016;62:1002–1008.
   PubMed Web of Science ®Google Scholar
• Joshi PP, Shegokar VR, Powar RM, et al. Human trypanosomiasis caused by Trypanosoma evansi in India: the first case report. Am J Trop Med Hyg. 2005;73:491–495.
   PubMed Web of Science ®Google Scholar
• Misra KK, Roy S, Choudhury A. Biology of Trypanosoma (Trypanozoon) evansi in experimental heterologous mammalian hosts. J Parasit Dis. 2016;40(3):1047–1061.
   PubMedGoogle Scholar
• Kurup S, Tewari A. Induction of protective immune response in mice by a DNA vaccine encoding Trypanosoma evansi beta tubulin gene. Vet Parasitol. 2012;187(1–2):9–16.
   PubMed Web of Science ®Google Scholar
• Faccio L, Da Silva AS, Gressler LT, et al. Susceptibility of Brazilian isolates of Trypanosoma evansi to suramin sodium: test in experimentally infected mice. Exp Parasitol. 2013;134(3):309–312.
   PubMed Web of Science ®Google Scholar
• Gourbal B, Pinaud S, Beckers GJM, et al. Innate immune memory: an evolutionary perspective. Immunol Rev. 2018;283(1):21–40.
   PubMed Web of Science ®Google Scholar
• Kawai T, Akira S. Pathogen recognition with Toll-like receptors. Curr Opin Immunol. 2005;17(4):338–344.
   PubMed Web of Science ®Google Scholar
• Janeway CA Jr., Medzhitov R. Innate Immune Recognition. Annu Rev Immunol. 2002;20(1):197–216.
   PubMed Web of Science ®Google Scholar
• Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol. 2004;4(7):499–511.
   PubMed Web of Science ®Google Scholar
• Souza COS, Gardinassi LG, Rodrigues V, et al. Monocyte and Macrophage-Mediated Pathology and protective immunity during schistosomiasis. Front Microbiol. 2020;11:1973.
   PubMed Web of Science ®Google Scholar
• Oliveira AC, Peixoto JR, de Arruda LB, et al. Expression of functional TLR4 confers proinflammatory responsiveness to trypanosoma cruzi glycoinositolphospholipids and higher resistance to infection with T. cruzi. J Immunol. 2004;173(9):5688–5696.
   PubMed Web of Science ®Google Scholar
• De Veer MJ, Curtis JM, Baldwin TM, et al. MyD88 is essential for clearance ofLeishmania major: possible role for lipophosphoglycan and Toll-like receptor 2 signaling. Eur J Immunol. 2003;33(10):2822–2831.
   PubMed Web of Science ®Google Scholar
• Srivastava S, Pandey SP, Jha MK, et al. Leishmania expressed lipophosphoglycan interacts with Toll-like receptor (TLR)-2 to decrease TLR-9 expression and reduce anti-Leishmanial responses. Clin Exp Immunol. 2013;172(3):403–409.
   PubMed Web of Science ®Google Scholar
• Campos MA, Closel M, Valente EP, et al. Impaired production of proinflammatory cytokines and host resistance to acute infection with Trypanosoma cruzi in mice lacking functional myeloid differentiation factor 88. J Immunol. 2004;172(3):1711–1718.
   PubMed Web of Science ®Google Scholar
• Ives A, Ronet C, Prevel F, et al. Leishmania RNA virus controls the severity of mucocutaneous leishmaniasis. Science. 2011;331(6018):775–778.
   PubMed Web of Science ®Google Scholar
• Zaborowski MP, Balaj L, Breakefield XO, et al. Extracellular vesicles: composition, biological relevance, and methods of study. Bioscience. 2015;65(8):783–797.
   PubMed Web of Science ®Google Scholar
• Nowacki FC, Swain MT, Klychnikov OI, et al. Protein and small non-coding RNA-enriched extracellular vesicles are released by the pathogenic blood fluke Schistosoma mansoni. J Extracell Vesicles. 2015;4(1):28665.
   PubMed Web of Science ®Google Scholar
• Schorey JS, Cheng Y, Singh PP, et al. Exosomes and other extracellular vesicles in host-pathogen interactions. EMBO Rep. 2015;16(1):24–43.
   PubMed Web of Science ®Google Scholar
• Bose S, Aggarwal S, Singh DV, et al. Extracellular vesicles: an emerging platform in gram-positive bacteria. Microb Cell. 2020;7(12):312–322.
   PubMed Web of Science ®Google Scholar
• Rodrigues ML, Nakayasu ES, Oliveira DL, et al. Extracellular vesicles produced by Cryptococcus neoformans contain protein components associated with virulence. Eukaryot Cell. 2008;7(1):58–67.
   PubMedGoogle Scholar
• Szempruch AJ, Dennison L, Kieft R, et al. Sending a message: extracellular vesicles of pathogenic protozoan parasites. Nature Rev Microbiol. 2016;14(11):669–675.
   PubMed Web of Science ®Google Scholar
• Coakley G, Maizels RM, Buck AH. Exosomes and other extracellular vesicles: the new communicators in parasite infections. Trends Parasitol. 2015;31(10):477–489.
   PubMed Web of Science ®Google Scholar
• Atayde VD, da Silva Lira Filho A, Chaparro V, et al. Exploitation of the Leishmania exosomal pathway by Leishmania RNA virus 1. Nat Microbiol. 2019;4(4):714–723.
   PubMed Web of Science ®Google Scholar
• Martin-Jaular L, Nakayasu ES, Ferrer M, et al. Exosomes from Plasmodium yoelii-infected reticulocytes protect mice from lethal infections. PLoS One. 2011;6(10):e26588.
   PubMed Web of Science ®Google Scholar
• Twu O, de Miguel N, Lustig G, et al. Trichomonas vaginalis exosomes deliver cargo to host cells and mediate host∶parasite interactions. PLoS Pathog. 2013;9(7):e1003482.
   PubMed Web of Science ®Google Scholar
• Li S, Gong PT, Tai LX, et al. Extracellular vesicles secreted by Neospora caninum are recognized by toll-like receptor 2 and modulate host cell innate immunity through the MAPK Signaling Pathway. Front Immunol. 2018;9:1633.
   Web of Science ®Google Scholar
• Tavares KC, Da Silva AS, Wolkmer P, et al. Cryopreservation of Trypanosoma evansi after DEAE-cellulose purification: evaluation of infective parameters. Res Vet Sci. 2011;90(2):257–259.
   PubMed Web of Science ®Google Scholar
• Pineda-Torra I, Gage M, De Juan A, et al. Isolation, culture, and polarization of murine bone marrow-derived and peritoneal macrophages. Methods Mol Biol. 2015;1339:101–109.
   PubMedGoogle Scholar
• Szempruch AJ, Sykes SE, Kieft R, et al. Extracellular vesicles from Trypanosoma brucei mediate virulence factor transfer and cause host anemia. Cell. 2016;164(1–2):246–257.
   PubMed Web of Science ®Google Scholar
• Aida Y, Pabst MJ. Removal of endotoxin from protein solutions by phase separation using Triton X-114. J Immunol Methods. 1990;132(2):191–195.
   PubMed Web of Science ®Google Scholar
• Cheng Y, Ren X, Zhang Y, et al. eEF-2 kinase dictates cross-talk between autophagy and apoptosis induced by Akt inhibition, thereby modulating cytotoxicity of novel Akt inhibitor MK-2206. Cancer Res. 2011;71(7):2654–2663.
   PubMed Web of Science ®Google Scholar
• Aliberti JC, Cardoso MA, Martins GA, et al. Interleukin-12 mediates resistance to Trypanosoma cruzi in mice and is produced by murine macrophages in response to live trypomastigotes. Infect Immun. 1996;64(6):1961–1967.
   PubMed Web of Science ®Google Scholar
• Wu H, Liu G, Shi M. Interferon Gamma in African trypanosome infections: friends or foes? Front Immunol. 2017;8:1105.
   PubMed Web of Science ®Google Scholar
• Vincendeau P, Bouteille B. Immunology and immunopathology of African trypanosomiasis. An Acad Bras Cienc. 2006;78(4):645–665.
   PubMed Web of Science ®Google Scholar
• Crawford AC, Lehtovirta-Morley LE, Alamir O, et al. Biphasic zinc compartmentalisation in a human fungal pathogen. PLoS Pathog. 2018;14(5):e1007013.
   PubMed Web of Science ®Google Scholar
• Taylor JE, Rudenko G. Switching trypanosome coats: what’s in the wardrobe? Trends Genet. 2006;22(11):614–620.
   PubMed Web of Science ®Google Scholar
• Tabel H, Wei G, Shi M. T cells and immunopathogenesis of experimental African trypanosomiasis. Immunol Rev. 2008;225(1):128–139.
   PubMedGoogle Scholar
• Stijlemans B, Caljon G, Van Den Abbeele J, et al. Immune Evasion Strategies of Trypanosoma brucei within the mammalian host: progression to pathogenicity. Front Immunol. 2016;7. DOI:10.3389/fimmu.2016.00233
   PubMed Web of Science ®Google Scholar
• Magez S, Torres JEP, Obishakin E, et al. Infections with extracellular trypanosomes require control by efficient innate immune mechanisms and can result in the destruction of the mammalian humoral immune system. Front Immunol. 2020;11. DOI:10.3389/fimmu.2020.00382
   Web of Science ®Google Scholar
• Kuriakose S, Onyilagha C, Singh R, et al. TLR-2 and MyD88-Dependent activation of MAPK and STAT proteins regulates proinflammatory cytokine response and immunity to experimental Trypanosoma congolense Infection. Front Immunol. 2019;10. DOI:10.3389/fimmu.2019.02673
   PubMed Web of Science ®Google Scholar
• Zheng H, Tan ZP, Zhou TL, et al. The TLR2 is activated by sporozoites and suppresses intrahepatic rodent malaria parasite development. Sci Rep. 2015;5(1). DOI:10.1038/srep18239
   Google Scholar
• Del Rio L, Butcher BA, Bennouna S, et al. Toxoplasma gondii triggers myeloid differentiation factor 88-Dependent IL-12 and Chemokine Ligand 2 (Monocyte Chemoattractant Protein 1) responses using distinct parasite molecules and host receptors. J Iimmunol. 2004;172(11):6954–6960.
   PubMed Web of Science ®Google Scholar
• Muraille E, De Trez C, Brait M, et al. Genetically resistant mice lacking MyD88-Adapter protein display a high susceptibility to Leishmania major Infection associated with a Polarized Th2 response. J Iimmunol. 2003;170(8):4237–4241.
   PubMed Web of Science ®Google Scholar
• Li X, Zhang X, Gong P, et al. TLR2−/− mice display decreased severity of giardiasis via enhanced proinflammatory cytokines production dependent on AKT signal pathway. Front Immunol. 2017;8. DOI:10.3389/fimmu.2017.01186
   Web of Science ®Google Scholar
• Guerra CS, Silva RM, Carvalho LO, et al. Histopathological analysis of initial cellular response in TLR-2 deficient mice experimentally infected by Leishmania (L.) amazonensis. Int J Exp Pathol. 2010;91(5):451–459.
   PubMed Web of Science ®Google Scholar
• Tarleton RL. Immune system recognition of Trypanosoma cruzi. Curr Opin Immunol. 2007;19(4):430–434.
   PubMed Web of Science ®Google Scholar
• Hunter CA, Slifer T, Araujo F. Interleukin-12-mediated resistance to Trypanosoma cruzi is dependent on tumor necrosis factor alpha and gamma interferon. Infect Immun. 1996;64(7):2381–2386.
   PubMed Web of Science ®Google Scholar
• Barkhuizen M, Magez S, Atkinson RA, et al. Interleukin-12p70-dependent interferon- gamma production is crucial for resistance in African trypanosomiasis. J Infect Dis. 2007;196:1253–1260.
   PubMed Web of Science ®Google Scholar
• Paim FC, Duarte MM, Costa MM, et al. Cytokines in rats experimentally infected with Trypanosoma evansi. Exp Parasitol. 2011;128:365–370.
   PubMed Web of Science ®Google Scholar
• Kaushik RS, Uzonna JE, Zhang Y, et al. Innate resistance to experimental African trypanosomiasis: differences in cytokine (TNF-alpha, IL-6, IL-10 and IL-12) production by bone marrow-derived macrophages from resistant and susceptible mice. Cytokine. 2000;12:1024–1034.
   PubMed Web of Science ®Google Scholar
• Truyens C, Torrico F, Angelo-Barrios A, et al. The cachexia associated with Trypanosoma cruzi acute infection in mice is attenuated by anti-TNF-alpha, but not by anti-IL-6 or anti-IFN-gamma antibodies. Parasite Immunol. 1995;17:561–568.
   PubMed Web of Science ®Google Scholar
• Colineau L, Clos J, Moon KM, et al. Leishmania donovani chaperonin 10 regulates parasite internalization and intracellular survival in human macrophages. Med Microbiol Immunol. 2017;206:235–257.
   PubMed Web of Science ®Google Scholar
• Dos-Santos AL, Carvalho-Kelly LF, Dick CF, et al. Innate immunomodulation to trypanosomatid parasite infections. Exp Parasitol. 2016;167:67–75.
   PubMed Web of Science ®Google Scholar
• Stijlemans B, De Baetselier P, Magez S, et al. African trypanosomiasis-associated anemia: the contribution of the interplay between parasites and the mononuclear phagocyte system. Front Immunol. 2018;9:218.
   Web of Science ®Google Scholar
• Mekata H, Konnai S, Mingala CN, et al. Kinetics of regulatory dendritic cells in inflammatory responses during Trypanosoma evansi infection. Parasite Immunol. 2012;34:318–329.
   PubMed Web of Science ®Google Scholar
• Farrar MA, Schreiber RD. The molecular cell biology of interferon-gamma and its receptor. Annu Rev Immunol. 1993;11:571–611.
   PubMed Web of Science ®Google Scholar
• Schroder K, Hertzog PJ, Ravasi T, et al. Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol. 2004;75:163–189.
   PubMed Web of Science ®Google Scholar
• Bafica A, Santiago HC, Goldszmid R, et al. Cutting edge: TLR9 and TLR2 signaling together account for MyD88-dependent control of parasitemia in Trypanosoma cruzi infection. J Immunol. 2006;177:3515–3519.
   PubMed Web of Science ®Google Scholar
• Da Silva HB, Fonseca R, Alvarez JM, et al. IFN-gamma priming effects on the maintenance of effector memory CD4(+) T Cells and on phagocyte function: evidences from infectious diseases. J Immunol Res. 2015. DOI:10.1155/2015/202816
   Web of Science ®Google Scholar
• Inoue S, Niikura M, Mineo S, et al. Roles of IFN-gamma and gammadelta T Cells in Protective immunity against blood-stage malaria. Front Immunol. 2013;4:258.
   PubMed Web of Science ®Google Scholar
• Ropert C, Gazzinelli RT. Regulatory role of Toll-like receptor 2 during infection with Trypanosoma cruzi. J Endotoxin Res. 2004;10:425–430.
   PubMedGoogle Scholar
• Bayer-Santos E, Aguilar-Bonavides C, Rodrigues SP, et al. Proteomic analysis of trypanosoma cruzi secretome: characterization of two populations of extracellular vesicles and soluble proteins. J Proteome Res. 2013;12:883–897.
   PubMed Web of Science ®Google Scholar
• Li Z, Wang CC. KMP-11, a basal body and flagellar protein, is required for cell division in Trypanosoma brucei. Eukaryot Cell. 2008;7:1941–1950.
   PubMedGoogle Scholar
• De Mendonca SC, Cysne-Finkelstein L, Matos DC. Kinetoplastid membrane protein-11 as a vaccine candidate and a virulence factor in Leishmania. Front Immunol. 2015;6:524.
   PubMed Web of Science ®Google Scholar