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

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Altan-Bonnet N. (2016). Extracellular vesicles are the Trojan horses of viral infection. 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. PubMed DOI PMC

Atayde V. D., Aslan H., Townsend S., Hassani K., Kamhawi S. and Olivier M. (2015). Exosome secretion by the parasitic protozoan 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. 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. 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. 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 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. PubMed DOI PMC

Browning R. and Karim S. (2013). RNA interference-mediated depletion of 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. 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. PubMed DOI PMC

Cheshomi H. and Matin M. M. (2018). Exosomes and their importance in metastasis, diagnosis, and therapy of colorectal cancer. 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. 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. 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. 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. 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 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 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 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. 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. 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 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. 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. 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. 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 PubMed DOI PMC

Goncalves M. F., Umezawa E. S., Katzin A. M., de Souza W., Alves M. J., Zingales B. and Colli W. (1991). 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 PubMed DOI PMC

Gross J. C., Chaudhary V., Bartscherer K. and Boutros M. (2012). Active Wnt proteins are secreted on exosomes. PubMed DOI

Hackenberg M. and Kotsyfakis M. (2018). Exosome-mediated pathogen transmission by arthropod vectors. PubMed DOI

Harischandra H., Yuan W., Loghry H. J., Zamanian M. and Kimber M. J. (2018). Profiling extracellular vesicle release by the filarial nematode 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 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. 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. PubMed DOI

Kaufer A., Ellis J., Stark D. and Barratt J. (2017). The evolution of trypanosomatid taxonomy. 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 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 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 PubMed DOI PMC

Leitner W. W., Wali T. and Costero-Saint Denis A. (2013). Is arthropod saliva the achilles’ heel of vector-borne diseases? 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. 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 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 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. 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. PubMed DOI PMC

Marti M. and Johnson P. J. (2016). Emerging roles for extracellular vesicles in parasitic infections. 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? 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. 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. PubMed DOI PMC

Nair S., Tang K. D., Kenny L. and Punyadeera C. (2018). Salivary exosomes as potential biomarkers in cancer. PubMed DOI

Neves R. F. C., Fernandes A. C. S., Meyer-Fernandes J. R. and Souto-Padrón T. (2014). 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 PubMed DOI PMC

Oberholzer M., Lopez M. A., McLelland B. T. and Hill K. L. (2010). Social motility in african trypanosomes. PubMed DOI PMC

Oliver J. D., Chavez A. S. O., Felsheim R. F., Kurtti T. J. and Munderloh U. G. (2015). An 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. PubMed DOI

Raab-Traub N. and Dittmer D. P. (2017). Viral effects on the content and function of extracellular vesicles. 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. 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 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. 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 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. PubMed DOI

Schorey J. S. and Harding C. V. (2016). Extracellular vesicles and infectious diseases: new complexity to an old story. 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. PubMed DOI PMC

Sedgwick A. E. and D'Souza-Schorey C. (2018). The biology of extracellular microvesicles. PubMed DOI PMC

Shaw D. K., Kotsyfakis M. and Pedra J. H. F. (2016). For whom the bell tolls (and Nods): spit-acular saliva. 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. 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 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). 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. 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. PubMed DOI PMC

Singh P. P., LeMaire C., Tan J. C., Zeng E. and Schorey J. S. (2011). Exosomes released from 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. PubMed DOI PMC

Smith V. L., Cheng Y., Bryant B. R. and Schorey J. S. (2017). Exosomes function in antigen presentation during an 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. 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. 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 PubMed DOI PMC

Théry C., Ostrowski M. and Segura E. (2009). Membrane vesicles as conveyors of immune responses. 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 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 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. 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). PubMed DOI

van Niel G., D'Angelo G. and Raposo G. (2018). Shedding light on the cell biology of extracellular vesicles. 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. 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. 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. 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 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. PubMed DOI PMC

WHO. (2017).

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. PubMed DOI PMC

Wyllie M. P. and Ramirez M. I. (2017). Microvesicles released during the interaction between 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. 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 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. 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. PubMed DOI PMC

Tick Salivary Compounds for Targeted Immunomodulatory Therapy