Vector-borne diseases cause over 700,000 deaths annually and represent 17% of all infectious illnesses worldwide. This public health menace highlights the importance of understanding how arthropod vectors, microbes and their mammalian hosts interact. Currently, an emphasis of the scientific enterprise is at the vector-host interface where human pathogens are acquired and transmitted. At this spatial junction, arthropod effector molecules are secreted, enabling microbial pathogenesis and disease. Extracellular vesicles manipulate signaling networks by carrying proteins, lipids, carbohydrates and regulatory nucleic acids. Therefore, they are well positioned to aid in cell-to-cell communication and mediate molecular interactions. This Review briefly discusses exosome and microvesicle biogenesis, their cargo, and the role that nanovesicles play during pathogen spread, host colonization and disease pathogenesis. We then focus on the role of extracellular vesicles in dictating microbial pathogenesis and host immunity during transmission of vector-borne pathogens.

Department of Microbiology and Immunology University of Maryland School of Medicine Baltimore MD 21201 USA

Department of Pathology Albert Einstein College of Medicine Bronx New York NY 10461 USA

Institute of Parasitology Biology Center of the Czech Academy of Sciences Ceske Budejovice 37005 Czech Republic

Zobrazit více v PubMed

Altan-Bonnet N. (2016). Extracellular vesicles are the Trojan horses of viral infection. Curr. Opin. Microbiol. 32, 77-81. 10.1016/j.mib.2016.05.004 PubMed DOI PMC

Arakelyan A., Fitzgerald W., Zicari S., Vanpouille C. and Margolis L. (2017). Extracellular vesicles carry HIV Env and facilitate HIV infection of human lymphoid tissue. Sci. Rep. 7, 1695 10.1038/s41598-017-01739-8 PubMed DOI PMC

Atayde V. D., Aslan H., Townsend S., Hassani K., Kamhawi S. and Olivier M. (2015). Exosome secretion by the parasitic protozoan Leishmania within the sand fly midgut. Cell Rep. 13, 957-967. 10.1016/j.celrep.2015.09.058 PubMed DOI PMC

Babatunde K. A., Mbagwu S., Hernández-Castañeda M. A., Adapa S. R., Walch M., Filgueira L., Falquet L., Jiang R. H. Y., Ghiran I. and Mantel P.-Y. (2018). Malaria infected red blood cells release small regulatory RNAs through extracellular vesicles. Sci. Rep. 8, 884 10.1038/s41598-018-19149-9 PubMed DOI PMC

Baietti M. F., Zhang Z., Mortier E., Melchior A., Degeest G., Geeraerts A., Ivarsson Y., Depoortere F., Coomans C., Vermeiren E. et al. (2012). Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat. Cell Biol. 14, 677-685. 10.1038/ncb2502 PubMed DOI

Banerjee S., Xie N., Cui H., Tan Z., Yang S., Icyuz M., Abraham E. and Liu G. (2013). MicroRNA let-7c regulates macrophage polarization. J. Immunol. 190, 6542-6549. 10.4049/jimmunol.1202496 PubMed DOI PMC

Bayer-Santos E., Aguilar-Bonavides C., Rodrigues S. P., Cordero E. M., Marques A. F., Varela-Ramirez A., Choi H., Yoshida N., da Silveira J. F. and Almeida I. C. (2013). Proteomic analysis of Trypanosoma cruzi secretome: characterization of two populations of extracellular vesicles and soluble proteins. J. Proteome Res. 12, 883-897. 10.1021/pr300947g PubMed DOI

Beer K. B., Rivas-Castillo J., Kuhn K., Fazeli G., Karmann B., Nance J. F., Stigloher C. and Wehman A. M. (2018). Extracellular vesicle budding is inhibited by redundant regulators of TAT-5 flippase localization and phospholipid asymmetry. Proc. Natl. Acad. Sci. USA 115, E1127-E1136. 10.1073/pnas.1714085115 PubMed DOI PMC

Browning R. and Karim S. (2013). RNA interference-mediated depletion of N-ethylmaleimide sensitive fusion protein and synaptosomal associated protein of 25 kDa results in the inhibition of blood feeding of the Gulf Coast tick, Amblyomma maculatum. Insect Mol. Biol. 22, 245-257. 10.1111/imb.12017 PubMed DOI PMC

Buck A. H., Coakley G., Simbari F., McSorley H. J., Quintana J. F., Le Bihan T., Kumar S., Abreu-Goodger C., Lear M., Harcus Y. et al. (2014). Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity. Nat. Commun. 5, 5488 10.1038/ncomms6488 PubMed DOI PMC

Bolukbasi M. F., Mizrak A., Ozdener G. B., Madlener S., Ströbel T., Erkan E. P., Fan J. B., Breakefield X. O. and Saydam O. (2012) miR-1289 and “Zipcode”-like sequence enrich mRNAs in microvesicles. Mol. Ther. Nucleic Acids1, e10 10.1038/mtna.2011.2 PubMed DOI PMC

Cheshomi H. and Matin M. M. (2018). Exosomes and their importance in metastasis, diagnosis, and therapy of colorectal cancer. J. Cell. Biochem. 23, 27582 10.1002/jcb.27582 PubMed DOI

Choi H. W., Suwanpradid J., Kim I. H., Staats H. F., Haniffa M., MacLeod A. S. and Abraham S. N. (2018). Perivascular dendritic cells elicit anaphylaxis by relaying allergens to mast cells via microvesicles. Science 362, eaao0666 10.1126/science.aao0666 PubMed DOI PMC

Clancy J. W., Sedgwick A., Rosse C., Muralidharan-Chari V., Raposo G., Method M., Chavrier P. and D'Souza-Schorey C. (2015). Regulated delivery of molecular cargo to invasive tumour-derived microvesicles. Nat. Commun. 6, 6919 10.1038/ncomms7919 PubMed DOI PMC

Coakley G., McCaskill J. L., Borger J. G., Simbari F., Robertson E., Millar M., Harcus Y., McSorley H. J., Maizels R. M. and Buck A. H. (2017). Extracellular vesicles from a helminth parasite suppress macrophage activation and constitute an effective vaccine for protective immunity. Cell Rep. 19, 1545-1557. 10.1016/j.celrep.2017.05.001 PubMed DOI PMC

Colombo M., Moita C., van Niel G., Kowal J., Vigneron J., Benaroch P., Manel N., Moita L. F., Théry C. and Raposo G. (2013). Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J. Cell Sci. 126, 5553-5565. 10.1242/jcs.128868 PubMed DOI

Cronemberger-Andrade A., Aragão-França L., de Araujo C. F., Rocha V. J., Borges-Silva M. C., Figueira C. P., Oliveira P. R., de Freitas L. A. R., Veras P. S. T. and Pontes-de-Carvalho L. (2014). Extracellular vesicles from Leishmania-infected macrophages confer an anti-infection cytokine-production profile to naïve macrophages. PLoS Negl. Trop. Dis. 8, e3161 10.1371/journal.pntd.0003161 PubMed DOI PMC

Diaz G., Wolfe L. M., Kruh-Garcia N. A. and Dobos K. M. (2016). Changes in the membrane-associated proteins of exosomes released from human macrophages after Mycobacterium tuberculosis infection. Sci. Rep. 6, 37975 10.1038/srep37975 PubMed DOI PMC

Díaz-Martín V., Manzano-Román R., Valero L., Oleaga A., Encinas-Grandes A. and Pérez-Sánchez R. (2013). An insight into the proteome of the saliva of the argasid tick Ornithodoros moubata reveals important differences in saliva protein composition between the sexes. J. Proteomics 80, 216-235. 10.1016/j.jprot.2013.01.015 PubMed DOI

Eichenberger R. M., Ryan S., Jones L., Buitrago G., Polster R., Montes de Oca M., Zuvelek J., Giacomin P. R., Dent L. A., Engwerda C. R. et al. (2018). Hookworm secreted extracellular vesicles interact with host cells and prevent inducible colitis in mice. Front. Immunol. 9, 850 10.3389/fimmu.2018.00850 PubMed DOI PMC

El-Assaad F., Wheway J., Hunt N. H., Grau G. E. R. and Combes V. (2014). Production, fate and pathogenicity of plasma microparticles in murine cerebral malaria. PLoS Pathog. 10, e1003839 10.1371/journal.ppat.1003839 PubMed DOI PMC

Eliaz D., Kannan S., Shaked H., Arvatz G., Tkacz I. D., Binder L., Waldman Ben-Asher H., Okalang U., Chikne V., Cohen-Chalamish S. et al. (2017). Exosome secretion affects social motility in Trypanosoma brucei. PLoS Pathog. 13, e1006245 10.1371/journal.ppat.1006245 PubMed DOI PMC

Fader C. M., Sánchez D. G., Mestre M. B. and Colombo M. I. (2009). TI-VAMP/VAMP7 and VAMP3/cellubrevin: two v-SNARE proteins involved in specific steps of the autophagy/multivesicular body pathways. Biochim. Biophys. Acta 1793, 1901-1916. 10.1016/j.bbamcr.2009.09.011 PubMed DOI

Feng Z., Hensley L., McKnight K. L., Hu F., Madden V., Ping L. F., Jeong S.-H., Walker C., Lanford R. E. and Lemon S. M. (2013). A pathogenic picornavirus acquires an envelope by hijacking cellular membranes. Nature 496, 367-371. 10.1038/nature12029 PubMed DOI PMC

Fleming A., Sampey G., Chung M.-C., Bailey C., van Hoek M. L., Kashanchi F. and Hakami R. M. (2014). The carrying pigeons of the cell: exosomes and their role in infectious diseases caused by human pathogens. Pathog. Dis. 71, 109-120. 10.1111/2049-632X.12135 PubMed DOI

Giri P. K., Kruh N. A., Dobos K. M. and Schorey J. S. (2010). Proteomic analysis identifies highly antigenic proteins in exosomes from M. tuberculosis-infected and culture filtrate protein-treated macrophages. Proteomics 10, 3190-3202. 10.1002/pmic.200900840 PubMed DOI PMC

Goncalves M. F., Umezawa E. S., Katzin A. M., de Souza W., Alves M. J., Zingales B. and Colli W. (1991). Trypanosoma cruzi: shedding of surface antigens as membrane vesicles. Exp. Parasitol. 72, 43-53. 10.1016/0014-4894(91)90119-H PubMed DOI

Gonçalves D. S., Ferreira M. S., Liedke S. C., Gomes K. X., de Oliveira G. A., Leão P. E. L., Cesar G. V., Seabra S. H., Cortines J. R., Casadevall A. et al. (2018). Extracellular vesicles and vesicle-free secretome of the protozoa Acanthamoeba castellanii under homeostasis and nutritional stress and their damaging potential to host cells. Virulence 9, 818-836. 10.1080/21505594.2018.1451184 PubMed DOI PMC

Gross J. C., Chaudhary V., Bartscherer K. and Boutros M. (2012). Active Wnt proteins are secreted on exosomes. Nat. Cell Biol. 14, 1036-1045. 10.1038/ncb2574 PubMed DOI

Hackenberg M. and Kotsyfakis M. (2018). Exosome-mediated pathogen transmission by arthropod vectors. Trends Parasitol. 34, 549-552. 10.1016/j.pt.2018.04.001 PubMed DOI

Harischandra H., Yuan W., Loghry H. J., Zamanian M. and Kimber M. J. (2018). Profiling extracellular vesicle release by the filarial nematode Brugia malayi reveals sex-specific differences in cargo and a sensitivity to ivermectin. PLoS Negl. Trop. Dis. 12, e0006438 10.1371/journal.pntd.0006438 PubMed DOI PMC

Hassani K., Shio M. T., Martel C., Faubert D. and Olivier M. (2014). Absence of metalloprotease GP63 alters the protein content of Leishmania exosomes. PLoS ONE 9, e95007 10.1371/journal.pone.0095007 PubMed DOI PMC

Hoshino A., Costa-Silva B., Shen T.-L., Rodrigues G., Hashimoto A., Tesic Mark M., Molina H., Kohsaka S., Di Giannatale A., Ceder S. et al. (2015). Tumour exosome integrins determine organotropic metastasis. Nature 527, 329-335. 10.1038/nature15756 PubMed DOI PMC

Karim S., Miller N. J., Valenzuela J., Sauer J. R. and Mather T. N. (2005). RNAi-mediated gene silencing to assess the role of synaptobrevin and cystatin in tick blood feeding. Biochem. Biophys. Res. Commun. 334, 1336-1342. 10.1016/j.bbrc.2005.07.036 PubMed DOI

Kaufer A., Ellis J., Stark D. and Barratt J. (2017). The evolution of trypanosomatid taxonomy. Parasit. Vectors 10, 287 10.1186/s13071-017-2204-7 PubMed DOI PMC

Kruh-Garcia N. A., Wolfe L. M., Chaisson L. H., Worodria W. O., Nahid P., Schorey J. S., Davis J. L. and Dobos K. M. (2014). Detection of Mycobacterium tuberculosis peptides in the exosomes of patients with active and latent M. tuberculosis infection using MRM-MS. PLoS ONE 9, e103811 10.1371/journal.pone.0103811 PubMed DOI PMC

Lambertz U., Oviedo Ovando M. E., Vasconcelos E. J., Unrau P. J., Myler P. J. and Reiner N. E. (2015). Small RNAs derived from tRNAs and rRNAs are highly enriched in exosomes from both old and new world Leishmania providing evidence for conserved exosomal RNA packaging. BMC Genomics 16, 151 10.1186/s12864-015-1260-7 PubMed DOI PMC

Leitherer S., Clos J., Liebler-Tenorio E. M., Schleicher U., Bogdan C. and Soulat D. (2017). Characterization of the protein tyrosine phosphatase LmPRL-1 secreted by Leishmania major via the exosome pathway. Infect. Immun. 85, 00084-17 10.1128/IAI.00084-17 PubMed DOI PMC

Leitner W. W., Wali T. and Costero-Saint Denis A. (2013). Is arthropod saliva the achilles’ heel of vector-borne diseases? Front. Immunol. 4, 255 10.3389/fimmu.2013.00255 PubMed DOI PMC

Li B., Antonyak M. A., Zhang J. and Cerione R. A. (2012). RhoA triggers a specific signaling pathway that generates transforming microvesicles in cancer cells. Oncogene 31, 4740-4749. 10.1038/onc.2011.636 PubMed DOI PMC

Lidani K. C. F., Bavia L., Ambrosio A. R. and de Messias-Reason I. J. (2017). The complement system: a prey of Trypanosoma cruzi. Front. Microbiol. 8, 607 10.3389/fmicb.2017.00607 PubMed DOI PMC

Lovo-Martins M. I., Malvezi A. D., Zanluqui N. G., Lucchetti B. F. C., Tatakihara V. L. H., Mörking P. A., de Oliveira A. G., Goldenberg S., Wowk P. F. and Pinge-Filho P. (2018). Extracellular vesicles shed by Trypanosoma cruzi potentiate infection and elicit lipid body formation and PGE2 production in murine macrophages. Front. Immunol. 9, 896 10.3389/fimmu.2018.00896 PubMed DOI PMC

Lunavat T. R., Cheng L., Kim D.-K., Bhadury J., Jang S. C., Lässer C., Sharples R. A., López M. D., Nilsson J., Gho Y. S. et al. (2015). Small RNA deep sequencing discriminates subsets of extracellular vesicles released by melanoma cells--evidence of unique microRNA cargos. RNA Biol. 12, 810-823. 10.1080/15476286.2015.1056975 PubMed DOI PMC

Mantel P.-Y., Hjelmqvist D., Walch M., Kharoubi-Hess S., Nilsson S., Ravel D., Ribeiro M., Grüring C., Ma S., Padmanabhan P. et al. (2016). Infected erythrocyte-derived extracellular vesicles alter vascular function via regulatory Ago2-miRNA complexes in malaria. Nat. Commun. 7, 12727 10.1038/ncomms12727 PubMed DOI PMC

Marti M. and Johnson P. J. (2016). Emerging roles for extracellular vesicles in parasitic infections. Curr. Opin. Microbiol. 32, 66-70. 10.1016/j.mib.2016.04.008 PubMed DOI PMC

McCarthy E. M., Wilkinson F. L., Parker B. and Alexander M. Y. (2016). Endothelial microparticles: Pathogenic or passive players in endothelial dysfunction in autoimmune rheumatic diseases? Vascul. Pharmacol. 86, 71-76. 10.1016/j.vph.2016.05.016 PubMed DOI

Moroishi T., Hayashi T., Pan W.-W., Fujita Y., Holt M. V., Qin J., Carson D. A. and Guan K.-L. (2016). The Hippo pathway kinases LATS1/2 suppress cancer immunity. Cell 167, 1525-1539.e17. 10.1016/j.cell.2016.11.005 PubMed DOI PMC

Nabhan J. F., Hu R., Oh R. S., Cohen S. N. and Lu Q. (2012). Formation and release of arrestin domain-containing protein 1-mediated microvesicles (ARMMs) at plasma membrane by recruitment of TSG101 protein. Proc. Natl. Acad. Sci. USA 109, 4146-4151. 10.1073/pnas.1200448109 PubMed DOI PMC

Nair S., Tang K. D., Kenny L. and Punyadeera C. (2018). Salivary exosomes as potential biomarkers in cancer. Oral Oncol. 84, 31-40. 10.1016/j.oraloncology.2018.07.001 PubMed DOI

Neves R. F. C., Fernandes A. C. S., Meyer-Fernandes J. R. and Souto-Padrón T. (2014). Trypanosoma cruzi-secreted vesicles have acid and alkaline phosphatase activities capable of increasing parasite adhesion and infection. Parasitol. Res. 113, 2961-2972. 10.1007/s00436-014-3958-x PubMed DOI

Nogueira P. M., Ribeiro K., Silveira A. C. O., Campos J. H., Martins-Filho O. A., Bela S. R., Campos M. A., Pessoa N. L., Colli W., Alves M. J. M. et al. (2015). Vesicles from different Trypanosoma cruzi strains trigger differential innate and chronic immune responses. J. Extracell Vesicles 4, 28734 10.3402/jev.v4.28734 PubMed DOI PMC

Oberholzer M., Lopez M. A., McLelland B. T. and Hill K. L. (2010). Social motility in african trypanosomes. PLoS Pathog. 6, e1000739 10.1371/journal.ppat.1000739 PubMed DOI PMC

Oliver J. D., Chavez A. S. O., Felsheim R. F., Kurtti T. J. and Munderloh U. G. (2015). An Ixodes scapularis cell line with a predominantly neuron-like phenotype. Exp. Appl. Acarol. 66, 427-442. 10.1007/s10493-015-9908-1 PubMed DOI PMC

Ostrowski M., Carmo N. B., Krumeich S., Fanget I., Raposo G., Savina A., Moita C. F., Schauer K., Hume A. N., Freitas R. P. et al. (2010). Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat. Cell Biol. 12, 19-30. 10.1038/ncb2000 PubMed DOI

Raab-Traub N. and Dittmer D. P. (2017). Viral effects on the content and function of extracellular vesicles. Nat. Rev. Microbiol. 15, 559-572. 10.1038/nrmicro.2017.60 PubMed DOI PMC

Regev-Rudzki N., Wilson D. W., Carvalho T. G., Sisquella X., Coleman B. M., Rug M., Bursac D., Angrisano F., Gee M., Hill A. F. et al. (2013). Cell-cell communication between malaria-infected red blood cells via exosome-like vesicles. Cell 153, 1120-1133. 10.1016/j.cell.2013.04.029 PubMed DOI

Ribeiro K. S., Vasconcellos C. I., Soares R. P., Mendes M. T., Ellis C. C., Aguilera-Flores M., de Almeida I. C., Schenkman S., Iwai L. K. and Torrecilhas A. C. (2018). Proteomic analysis reveals different composition of extracellular vesicles released by two Trypanosoma cruzi strains associated with their distinct interaction with host cells. J. Extracell Vesicles 7, 1463779 10.1080/20013078.2018.1463779 PubMed DOI PMC

Sahu R., Kaushik S., Clement C. C., Cannizzo E. S., Scharf B., Follenzi A., Potolicchio I., Nieves E., Cuervo A. M. and Santambrogio L. (2011). Microautophagy of cytosolic proteins by late endosomes. Dev. Cell 20, 131-139. 10.1016/j.devcel.2010.12.003 PubMed DOI PMC

Sampaio N. G., Emery S. J., Garnham A. L., Tan Q. Y., Sisquella X., Pimentel M. A., Jex A. R., Regev-Rudzki N., Schofield L. and Eriksson E. M. (2018). Extracellular vesicles from early stage Plasmodium falciparum-infected red blood cells contain PfEMP1 and induce transcriptional changes in human monocytes. Cell. Microbiol. 20, e12822 10.1111/cmi.12822 PubMed DOI

Santangelo L., Giurato G., Cicchini C., Montaldo C., Mancone C., Tarallo R., Battistelli C., Alonzi T., Weisz A. and Tripodi M. (2016). The RNA-binding protein SYNCRIP is a component of the hepatocyte exosomal machinery controlling microRNA sorting. Cell Rep. 17, 799-808. 10.1016/j.celrep.2016.09.031 PubMed DOI

Schorey J. S. and Harding C. V. (2016). Extracellular vesicles and infectious diseases: new complexity to an old story. J. Clin. Invest. 126, 1181-1189. 10.1172/JCI81132 PubMed DOI PMC

Schorey J. S., Cheng Y., Singh P. P. and Smith V. L. (2015). Exosomes and other extracellular vesicles in host-pathogen interactions. EMBO Rep. 16, 24-43. 10.15252/embr.201439363 PubMed DOI PMC

Sedgwick A. E. and D'Souza-Schorey C. (2018). The biology of extracellular microvesicles. Traffic 19, 319-327. 10.1111/tra.12558 PubMed DOI PMC

Shaw D. K., Kotsyfakis M. and Pedra J. H. F. (2016). For whom the bell tolls (and Nods): spit-acular saliva. Curr. Trop. Med. Rep. 3, 40-50. 10.1007/s40475-016-0072-4 PubMed DOI PMC

Shurtleff M. J., Temoche-Diaz M. M., Karfilis K. V., Ri S. and Schekman R. (2016). Y-box protein 1 is required to sort microRNAs into exosomes in cells and in a cell-free reaction. eLife 5, 19276 10.7554/eLife.19276 PubMed DOI PMC

Silverman J. M., Clos J., de'Oliveira C. C., Shirvani O., Fang Y., Wang C., Foster L. J. and Reiner N. E. (2010a). An exosome-based secretion pathway is responsible for protein export from Leishmania and communication with macrophages. J. Cell Sci. 123, 842-852. 10.1242/jcs.056465 PubMed DOI

Silverman J. M., Clos J., Horakova E., Wang A. Y., Wiesgigl M., Kelly I., Lynn M. A., McMaster W. R., Foster L. J., Levings M. K. et al. (2010b). Leishmania exosomes modulate innate and adaptive immune responses through effects on monocytes and dendritic cells. J. Immunol. 185, 5011-5022. 10.4049/jimmunol.1000541 PubMed DOI

Simbari F., McCaskill J., Coakley G., Millar M., Maizels R. M., Fabriás G., Casas J. and Buck A. H. (2016). Plasmalogen enrichment in exosomes secreted by a nematode parasite versus those derived from its mouse host: implications for exosome stability and biology. J. Extracell Vesicles 5, 30741 10.3402/jev.v5.30741 PubMed DOI PMC

Šimo L., Kazimirova M., Richardson J. and Bonnet S. I. (2017). The essential role of tick salivary glands and saliva in tick feeding and pathogen transmission. Front. Cell Infect. Microbiol. 7, 281 10.3389/fcimb.2017.00281 PubMed DOI PMC

Singh P. P., LeMaire C., Tan J. C., Zeng E. and Schorey J. S. (2011). Exosomes released from M. tuberculosis infected cells can suppress IFN-γ mediated activation of naïve macrophages. PLoS ONE 6, e18564 10.1371/journal.pone.0018564 PubMed DOI PMC

Sisquella X., Ofir-Birin Y., Pimentel M. A., Cheng L., Abou Karam P., Sampaio N. G., Penington J. S., Connolly D., Giladi T., Scicluna B. J. et al. (2017). Malaria parasite DNA-harbouring vesicles activate cytosolic immune sensors. Nat. Commun. 8, 1985 10.1038/s41467-017-02083-1 PubMed DOI PMC

Smith V. L., Cheng Y., Bryant B. R. and Schorey J. S. (2017). Exosomes function in antigen presentation during an in vivo Mycobacterium tuberculosis infection. Sci. Rep. 7, 43578 10.1038/srep43578 PubMed DOI PMC

Szempruch A. J., Sykes S.E., Kieft R., Dennison L., Becker A. C., Gartrell A., Martin W. J., Nakayasu E. S., Almeida I. C., Hajduk S. L. and Harrington J. M. (2016). Extracellular vesicles from Trypanosoma brucei mediate virulence factor transfer and cause host anemia. Cell 164, 246-257. 10.1016/j.cell.2015.11.051 PubMed DOI PMC

Tamai K., Tanaka N., Nakano T., Kakazu E., Kondo Y., Inoue J., Shiina M., Fukushima K., Hoshino T., Sano K. et al. (2010). Exosome secretion of dendritic cells is regulated by Hrs, an ESCRT-0 protein. Biochem. Biophys. Res. Commun. 399, 384-390. 10.1016/j.bbrc.2010.07.083 PubMed DOI

Teng G.-G., Wang W.-H., Dai Y., Wang S.-J., Chu Y.-X. and Li J. (2013). Let-7b is involved in the inflammation and immune responses associated with Helicobacter pylori infection by targeting Toll-like receptor 4. PLoS ONE 8, e56709 10.1371/journal.pone.0056709 PubMed DOI PMC

Théry C., Ostrowski M. and Segura E. (2009). Membrane vesicles as conveyors of immune responses. Nat. Rev. Immunol. 9, 581-593. 10.1038/nri2567 PubMed DOI

Tirloni L., Reck J., Terra R. M. S., Martins J. R., Mulenga A., Sherman N. E., Fox J. W., Yates J. R. III, Termignoni C., Pinto A. F. M. et al. (2014). Proteomic analysis of cattle tick Rhipicephalus (Boophilus) microplus saliva: a comparison between partially and fully engorged females. PLoS ONE 9, e94831 10.1371/journal.pone.0094831 PubMed DOI PMC

Tirloni L., Islam M. S., Kim T. K., Diedrich J. K., Yates J. R. III, Pinto A. F. M., Mulenga A., You M.-J. and Da Silva Vaz I. Jr (2015). Saliva from nymph and adult females of Haemaphysalis longicornis: a proteomic study. Parasit. Vectors 8, 338 10.1186/s13071-015-0918-y PubMed DOI PMC

Trajkovic K., Hsu C., Chiantia S., Rajendran L., Wenzel D., Wieland F., Schwille P., Brugger B. and Simons M. (2008). Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319, 1244-1247. 10.1126/science.1153124 PubMed DOI

Trocoli Torrecilhas A. C., Tonelli R. R., Pavanelli W. R., da Silva J. S., Schumacher R. I., de Souza W., Cunha e Silva N., de Almeida Abrahamsohn I., Colli W. and Manso Alves M. J. (2009). Trypanosoma cruzi: parasite shed vesicles increase heart parasitism and generate an intense inflammatory response. Microbes Infect. 11, 29-39. 10.1016/j.micinf.2008.10.003 PubMed DOI

van Niel G., D'Angelo G. and Raposo G. (2018). Shedding light on the cell biology of extracellular vesicles. Nat. Rev. Mol. Cell Biol. 19, 213-228. 10.1038/nrm.2017.125 PubMed DOI

Villarreal A. M., Adamson S. W., Browning R. E., Budachetri K., Sajid M. S. and Karim S. (2013). Molecular characterization and functional significance of the Vti family of SNARE proteins in tick salivary glands. Insect Biochem. Mol. Biol. 43, 483-493. 10.1016/j.ibmb.2013.03.003 PubMed DOI PMC

Villarroya-Beltri C., Gutiérrez-Vázquez C., Sánchez-Cabo F., Pérez-Hernández D., Vázquez J., Martin-Cofreces N., Martinez-Herrera D. J., Pascual-Montano A., Mittelbrunn M. and Sánchez-Madrid F. (2013). Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat. Commun. 4, 2980 10.1038/ncomms3980 PubMed DOI PMC

Vora A., Zhou W., Londono-Renteria B., Woodson M., Sherman M. B., Colpitts T. M., Neelakanta G. and Sultana H. (2018). Arthropod EVs mediate dengue virus transmission through interaction with a tetraspanin domain containing glycoprotein Tsp29Fb. Proc. Natl. Acad. Sci. USA 115, E6604-E6613. 10.1073/pnas.1720125115 PubMed DOI PMC

Wang Z., Xi J., Hao X., Deng W., Liu J., Wei C., Gao Y., Zhang L. and Wang H. (2017). Red blood cells release microparticles containing human argonaute 2 and miRNAs to target genes of Plasmodium falciparum. Emerg. Microbes Infect. 6, 1-11. 10.1038/emi.2017.63 PubMed DOI PMC

Wei Y., Wang D., Jin F., Bian Z., Li L., Liang H., Li M., Shi L., Pan C., Zhu D. et al. (2017). Pyruvate kinase type M2 promotes tumour cell exosome release via phosphorylating synaptosome-associated protein 23. Nat. Commun. 8, 14041 10.1038/ncomms14041 PubMed DOI PMC

WHO. (2017). Vector-Borne Diseases. WHO.

Willms E., Johansson H. J., Mäger I., Lee Y., Blomberg K. E. M., Sadik M., Alaarg A., Smith C. I. E., Lehtiö J., El Andaloussi S. et al. (2016). Cells release subpopulations of exosomes with distinct molecular and biological properties. Sci. Rep. 6, 22519 10.1038/srep22519 PubMed DOI PMC

Wyllie M. P. and Ramirez M. I. (2017). Microvesicles released during the interaction between Trypanosoma cruzi TcI and TcII strains and host blood cells inhibit complement system and increase the infectivity of metacyclic forms of host cells in a strain-independent process. Pathog. Dis. 75, ftx077 10.1093/femspd/ftx077 PubMed DOI

Xu B., Fu Y., Liu Y., Agvanian S., Wirka R. C., Baum R., Zhou K., Shaw R. M. and Hong T. T. (2017). The ESCRT-III pathway facilitates cardiomyocyte release of cBIN1-containing microparticles. PLoS Biol. 15, e2002354 10.1371/journal.pbio.2002354 PubMed DOI PMC

Zamanian M., Fraser L. M., Agbedanu P. N., Harischandra H., Moorhead A. R., Day T. A., Bartholomay L. C. and Kimber M. J. (2015). Release of Small RNA-containing Exosome-like vesicles from the human filarial parasite Brugia malayi. PLoS Negl. Trop. Dis. 9, e0004069 10.1371/journal.pntd.0004069 PubMed DOI PMC

Zhang H., Freitas D., Kim H. S., Fabijanic K., Li Z., Chen H., Mark M. T., Molina H., Martin A. B., Bojmar L. et al. (2018). Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation. Nat. Cell Biol. 20, 332-343. 10.1038/s41556-018-0040-4 PubMed DOI PMC

Zhou W., Woodson M., Neupane B., Bai F., Sherman M. B., Choi K. H., Neelakanta G. and Sultana H. (2018). Exosomes serve as novel modes of tick-borne flavivirus transmission from arthropod to human cells and facilitates dissemination of viral RNA and proteins to the vertebrate neuronal cells. PLoS Pathog. 14, e1006764 10.1371/journal.ppat.1006764 PubMed DOI PMC

Tick Salivary Compounds for Targeted Immunomodulatory Therapy