Genel Bakış: Eksozomlar ve Bazı Parazit Protozoon Enfeksiyonlardaki Rolleri

Yıl 2018, Cilt: 15 Sayı: 2, 179 - 189, 15.08.2018

Abdullah İnci , Mübeccel Okur , Önder Düzlü , Alparslan Yıldırım

Öz

Ekstraselüler veziküller (EVs), eksozomlar da dahil olmak üzere hücreler arası doğrudan temas olmadan bilgi alış verişini mümkün kılan hücresel iletişimin temel araçlarından biri olarak bilinmektedirler. Eksozomlar, multivezikül cisimlerin (MVBs) plazma membranı ile kaynaşmasından sonra salınan, 30-100 nm çapında endositik kökenli nano keseciklerdir. EV'ler, çok yakın zamana kadar sadece hücresel metabolizmanın bir yan ürünü olarak görülürlerdi. An-cak son zamanlarda yapılan yeni keşifler ve üretilen yeni bilgiler bu algının değişmesine yol açmıştır. Bu yeni keşiflerde EV’lerin hücre-hücre iletişimi, sinyal iletimi, genetik materyallerin taşınması ve immün yanıt modülasyonu gibi geniş bir biyolojik aktivite yelpazesinde yer aldıkları gösterilmiştir. Farklı kökenlere sahip olan bu veziküller, düzenleyebildikleri proteinler, DNA, mRNA'lar ve miRNA'lar gibi biyoaktif molekülleri kendi kargolarıyla hedef hücrelere taşırlar ve hastalık patogenezinde de önemli rol oynarlar. Yakın zamandaki çalışmalar, Malaria, Chagas hastalığı ve uyku hastalığı gibi insan hastalıklarından sorumlu olanlar da dahil olmak üzere hücre içi ve hücre dışı gelişim aşamalarında protozoon parazitlerin de benzer mekanizmaları kullandıkları gösterilmiştir. Protozoon parazitler, kendi popülasyonları içerisinde iletişim kurmak, büyümeyi teşvik etmek, bulaşmaya neden olmak, konağın bağışıklık sisteminden kaçmak ve mikro çevreyi manipüle etmek için hücre dışı vezikülleri salgılamaktadırlar. Mevcut veriler ışığında, hastalıkların teşhisinde bir marker, tedavide hedeflenen bir terapötik ajan olarak görülmenin yanında konak patojen ilişkisi, ilaç dirençliliği ve aşı geliştirilmesinde kullanılabileceklerine dair geniş ve önemli bir bakış açısı sağlamıştır. Bu derlemede eksozomların biyogenezi, kompozisyonu ve bazı protozoon infeksiyonlardaki farklı rolleri üzerine güncel bilgilerin sunulması amaç-lanmıştır.

Anahtar Kelimeler

Eksozomlar, ekstraselüler veziküller, parazit, protozoon

Kaynakça

• 1. Admyre C, Johansson SM, Qazi KR, Filen JJ, Lahesmaa R, Norman M, Neve EP, Scheynius A, Gabrielsson S. Exosomes with immune modulatory features are present in human breast milk. J Immunol 2007; 179(3): 1969-78. 2. Aline F, Bout D, Amigorena S, Roingeard P, Dimier-Poisson I. Toxoplasma gondii antigen-pulsed-dendritic cell-derived exosomes induce a protective immune response against T. gondii infection. Infect Immun 2004; 72(7): 4127-37. 3. Atayde VD, Aslan H, Townsend S, Hassani K, Kamhawi S, Olivier M. Exosome secretion by the parasitic protozoan Leishmania within the sand fly midgut. Cell Rep 2015; 13(5): 957-67. 4. Bayer-Santos E, Lima FM, Ruiz JC, Almeida IC, da Silveira JF. Characterization of the small RNA content of Trypanosoma cruzi extracellular vesicles. Mol Biochem Parasitol 2014;193(2): 71-4. 5. Bhatnagar S, Shinagawa K, Castellino FJ, Schorey JS. Exosomes released from macrophages infected with intracellular pathogens stimulate a proinflammatory response in vitro and in vivo. Blood 2007; 110(9): 3234-44. 6. Bobrie A, Colombo M, Raposo G, Théry C. Exosome secretion: Molecular mechanisms and roles in immune responses. Traffic 2011; 12(12): 1659-68. 7. Buzas EI, György B, György N, Falus A, Gay S. Emerging role of extracellular vesicles in inflammatory diseases. Nat Rev Rheumatol 2014; 10(6): 356-64. 8. Campos FM, Franklin BS, Teixeira-Carvalho A, Filho AL, de Paula SC, Fontes CJ, Brito CF, Carvalho LH. Augmented plasma microparticles during acute Plasmodium vivax infection. Malar J 2010; 9(1): 327. 9.Campos JH, Soares RP, Ribeiro K, Andrade AC, Batista WL, Torrecilhas AC. Extracellular vesicles: Role in inflammatory responses and potential uses in vaccination in cancer and infectious diseases. J Immunol Res 2015; Article ID: 832057. 10. Cestari I, Ansa-Addo E, Deolindo P, Inal JM, Ramirez MI. Trypanosoma cruzi immune evasion mediated by host cell-derived microvesicles. J Immunol 2012; 188(4): 1942-52. 11. Choi DS, Lee JM, Park GW, Lim HW, Bang JY, Kim YK, Kwon KH, Kwon HJ, Kim KP, Gho YS. Proteomic analysis of microvesicles derived from human colorectal cancer cells. J Proteome Res 2007; 6(12): 4646-55. 12. Chu Z, Witte DP, Qi X. Saposin C-LBPA interaction in late-endosomes/lysosomes. Exp Cell Res 2005; 303(2): 300-7. 13. Colombo M, Raposo G, Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol 2014; 30: 255-89. 14. Coltel N, Combes V, Wassmer SC, Chimini G, Grau GE. Cell vesiculation and immunopathology: Implications in cerebral malaria. Microbes Infect. 2006; 8(8): 2305-16. 15. Conde-Vancells J, Rodriguez-Suarez E, Embade N, Gil D, Matthiesen R, Valle M, Elortza F, Lu SC, Mato JM, Falcon-Perez JM. Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes. J Proteome Res 2008; 7(12): 5157-66. 16. Corbeel L, Freson K. Rab proteins and Rab-associated proteins: Major actors in themechanismof protein-trafficking disorders. Eur J Pediatr 2008; 167(7): 723-9. 17.Couper KN, Barnes T, Hafalla JC, Combes V, Ryffel B, Secher T, Grau GE, Riley EM, de Souza JB Parasite-derived plasma microparticles contribute significantly to malaria infection-induced inflammation through potent macrophage stimulation. PLoS Pathog 2010; 29; 6(1): e1000744. 18.Deolindo P, Evans-Osses I, Ramirez MI. Microvesicles and exosomes as vehicles between protozoan and host cell communication. Biochem Soc Trans 2013; 41(1): 252-7. 19. El Andaloussi S, Mäger I, Breakefield XO, Wood MJ. Extracellular vesicles: Biology and emerging therapeutic opportunities. Nat Rev Drug Discov 2013; 12(5): 347-57. 20. Fevrier B, Vilette D, Archer F, Loew D, Faigle W, Vidal M, Laude H, Raposo G. Cells release prions in association with exosomes. Proc Natl Acad Sci USA 2004; 101(26): 9683-8. 21. Futter CE, White IJ. Annexins and endocytosis. Traffic 2007; 8(8): 951-8. 22. Gonzales PA, Pisitkun T, Hoffert JD, Tchapyjnikov D, Star RA, Kleta R, Wang NS, Knepper MA. Large-scale proteomics and phosphoproteomics of urinary exosomes. J Am Soc Nephrol 2009; 20(2): 363-79. 23. Gonzalez-Begne M, Lu B, Han X, Hagen FK, Hand AR, Melvin JE, Yates JR. Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT). J Proteome Res 2008; 8(3): 1304-14. 24. Graner MW, Alzate O, Dechkovskaia AM, Keene JD, Sampson JH, Mitchell DA, Bigner DD. Proteomic and immunologic analyses of brain tumor exosomes. FASEB J 2009; 23(5): 1541-57. 25. Gutiérrez-Vázquez C, Villarroya-Beltri C, Mittelbrunn M, Sánchez-Madrid F. Transfer of extracellular vesicles during immune cell-cell interactions. Immunol Rev 2013; 251(1): 125-42. 26.Hassani K, Olivier M. Immunomodulatory impact of Leishmania-induced macrophage exosomes: a comparative proteomic and functional analysis. PLoS Negl Trop Dis 2013; 7(5): e2185. 27. Hegmans JP, Bard MP, Hemmes A, Luider TM, Kleijmeer MJ, Prins JB, Zitvogel L, Burgers SA, Hoogsteden HC, Lambrecht BN. Proteomic analysis of exosomes secreted by human mesothelioma cells. Am J Pathol 2004; 164(5): 1807-15. 28. Hu G, Gong AY, Roth AL, Huang BQ, Ward HD, Zhu G, Larusso NF, Hanson ND, Chen XM. Release of luminal exosomes contributes to TLR4-mediated epithelial antimicrobial defense. PLoS Pathog 2013; 9(4): e1003261. 29. İnci A, Bişkin Z. Toll-like reseptörler ve protozoon enfeksiyonlarındaki rolleri. Erciyes Üniv Vet Fak Derg 2007; 4(2): 121-8. 30. İnci A, Düzlü Ö. Vektörler ve vektörlerle bulaşan hastalıklar. Erciyes Üniv Vet Fak Derg 2009; 6(1): 53-63. 31. İnci A, İça A, Yıldırım A, Düzlü Ö. Memelilerin (yabani) önemli paraziter hastalıkları- I: Protozoon enfeksiyonları. Erciyes Üniv Vet Fak Derg 2008; 5(1): 51-60. 32. İnci A, Şahingöz Demirpolat G, Yıldırım A, Düzlü Ö. Apicomplexan protozoonlarda apicoplast. Erciyes Üniv Vet Fak Derg 2017; 14(1): 49-59. 33. İnci A, Uyanık F. Babesia Türlerinin Moleküler Biyolojisi. Özcel MA, Tanyüksel M, Eren H. eds. Moleküler Parazitoloji. İzmir: Türkiye Parazitoloji Derneği Yayınları, 2009; ss. 549-82. 34. İnci A, Yavuz A, Yıldırım A, Düzlü Ö, Bişkin Z. Sığır theileriosis’inde metastaz. Erciyes Üniv Vet Fak Derg 2012; 9(2): 113-22. 35. İnci A, Yazar S, Tunçbilek AS, Canhilal R, Doğanay M, Aydın L, Aktaş M, Vatansever Z, Özdarendeli A, Özbel Y, Yıldırım A, Düzlü Ö. Vectors and vector-borne diseases in Turkey. Ankara Üniv Vet Fak Derg 2013; 60: 281-96. 36. İnci A, Yıldırım A, Düzlü Ö, Doğanay M, Aksoy S. Tick-borne diseases in Turkey: A review based on one health perspective. PLoS Negl Trop Dis 2016; 10(12): e0005021. 37. İnci A, Yıldırım A, Düzlü Ö. The current status of ticks in Turkey: A 100-year period review from 1916 to 2016. Turkiye Parazitol Derg. 2016; 40(3): 152-57. 38. Ji H, Erfani N, Tauro BJ, Kapp EA, Zhu HJ, Moritz RL, LimJW, Simpson RJ. Difference gel electrophoresis analysis of ras-transformed fibroblast cell-derived exosomes. Electrophoresis 2008; 29(12): 2660-71. 39. Keller S, Sanderson MP, Stoeck A, Altevogt P. Exosomes: From biogenesis and secretion to biological function. Immunol Lett 2006; 107(2): 102-8. 40. Kesimer M, Scull M, Brighton B, Demaria G, Burns K, O'Neal W, Pickles RJ, Sheehan JK. Characterization of exosome-like vesicles released from human tracheobronchial ciliated epithelium: A possible role in innate defense. FASEB J 2009; 23(6): 1858-68. 41.Ko J, Carpenter E, Issadore D. Detection and isolation of circulating exosomes and microvesicles for cancer monitoring and diagnostics using micro-/nano-based devices. Analyst 2016; 141(2): 450-60. 42. Kobayashi T, Gu F, Gruenberg J. Lipids, lipid domains and lipid-protein interactions in endocytic membrane traffic. Semin Cell Dev Biol 1998; 9(5): 517-26. 43. Krämer-Albers EM, Bretz N, Tenzer S, Winterstein C, Möbius W, Berger H, Nave KA, Schild H, Trotter J. Oligodendrocytes secrete exosomes containing major myelin and stress-protective proteins: trophic support for axons? Proteomics Clin Appl 2007; 1(11): 1446-61. 44. Kuehn MJ, Kesty NC. Bacterial outer membrane vesicles and the hostpathogen interaction. Genes Dev 2005; 19(22): 2645-55. 45. Laulagnier K, Motta C, Hamdi S, Roy S, Fauvelle F, Pageaux JF, Kobayashi T, Salles JP, Perret B, Bonnerot C, Record M. Mast cell- and dendritic cell-derived exosomes display a specific lipid composition and an unusual membrane organization. Biochem J 2004; 380(1): 161-71. 46. Looze C, Yui D, Leung L, InghamM, Kaler M, Yao X, Wu WW, Shen RF, Daniels MP, Levine SJ. Proteomic profiling of human plasma exosomes identifies PPARgamma as an exosome-associated protein. Biochem Biophys Res Commun 2009; 378(3): 433-8. 47. Mantel PY, Marti M. The role of extracellular vesicles in Plasmodium and other protozoan parasites. Cell Microbiol 2014; 16(3): 344–54. 48.Mantel PY, Hoang AN, Goldowitz I, Potashnikova D, Hamza B, Vorobjev I, Ghiran I, Toner M, Irimia D, Ivanov AR, Barteneva N, Marti M. Malaria-infected erythrocyte-derived microvesicles mediate cellular communication within the parasite population and with the host immune system. Cell Host Microbe 2013; 13(5): 521-34. 49. Marcilla A, Martin-Jaular L, Trelis M, de Menezes-Neto A, Osuna A, Bernal D, Fernandez-Becerra C, Almeida IC, Del Portillo HA. Extracellular vesicles in parasitic diseases. J Extracell Vesicles 2014; 3(1): 25040. 50. Marcilla A, Trelis M, Cortés A, Sotillo J, Cantalapiedra F, Minguez MT, Valero ML, Sánchez del Pino MM, Muñoz-Antoli C, Toledo R, Bernal D. Extracellular vesicles from parasitic helminths contain specific excretory/secretory proteins and are internalized in intestinal host cells. PLoS One 2012; 7(9): e45974. 51. Marti M, Johnson PJ. Emerging roles for extracellular vesicles in parasitic infections. Curr Opin Microbiol 2016; 32: 66-70. 52. Martin-Jaular L, Nakayasu ES, Ferrer M, Almeida IC, Del Portillo HA. Exosomes from Plasmodium yoelii-infected reticulocytes protect mice from lethal infections. PLoS One 2011; 6(10): e26588. 53. Mathivanan S, Ji H, Simpson RJ. Extracellular organelles important in intercellular communication. J Proteomics 2010; 73(10); 1907-20. 54. Mathivanan S, Lim JW, Tauro BJ, Ji H, Moritz RL, Simpson RJ. Proteomic analysis of A33-immunoaffinity-purified exosomes released from the human colon tumor cell line LIM1215 reveals a tissue-specific protein signature. Mol Cell Proteomics 2009; 9(2): 197-208. 55. Mears R, Craven RA, Hanrahan S, Totty N, Upton C, Young SL, Patel P, Selby PJ, Banks RE. Proteomic analysis of melanomaderived exosomes by two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. Proteomics 2004; 4(12): 4019-31. 56. Nantakomol D, Dondorp AM, Krudsood S, Udomsangpetch R, Pattanapanyasat K, Combes V, Grau GE, White NJ, Viriyavejakul P, Day NP, Chotivanich K. Circulating red cell derived microparticles in human malaria. J Infect Dis 2011; 203(5): 700-6. 57. Pan BT, Johnstone RM. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: Selective externalization of the receptor. Cell 1983; 33(3): 967-78. 58. Pankoui Mfonkeu JB, Gouado I, Fotso Kuaté H, Zambou O, Amvam Zollo PH, Grau GE, Combes V. Elevated cell-specific microparticles are a biological marker for cerebral dysfunctions in human severe malaria. PLoS One 2010; 5: e13415. 59. Paschon V, Takada SH, Ikebara JM, Sousa E, Raeisossadati R, Ulrich H, Kihara AH. Interplay between exosomes, micrornas and toll-like receptors in brain disorders. Mol Neurobiol 2016; 53(3): 2016-28. 60. Pisitkun T, Shen RF, Knepper MA. Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci USA 2004;101(36):13368-73. 61. Pope SM, Lasser C. Toxoplasma gondii infection of fibroblasts causes the production of exosome-like vesicles containing a unique array of mRNA and miRNA transcripts compared to serum starvation. J Extracell Vesicles 2013; 2: 22484. 62. Potolicchio I, Carven GJ, Xu X, Stipp C, Riese RJ, Stern LJ, Santambrogio L. Proteomic analysis of microglia-derived exosomes: metabolic role of the aminopeptidase CD13 in neuropeptide catabolism. J Immunol 2005; 175 (4): 2237-43. 63. Raposo G, Stoorvogel W. Extracellular vesicles: Exosomes, microvesicles, and friends. J Cell Biol 2013; 200(4): 373-83. 64. Ravindran S, Boothroyd JC. Secretion of proteins into host cells by apicomplexan parasites. Traffic 2008; 9(5): 647-56. 65. Regev-Rudzki N, Wilson DW, Carvalho TG, Sisquella X, Coleman BM, Rug M, Bursac D, Angrisano F, Gee M, Hill AF, Baum J, Cowman AF. Cell-cell communication between malaria-infected red blood cells via exosome-like vesicles. Cell 2013; 153(5): 1120-33. 66. Silverman JM, Clos J, de'Oliveira CC, Shirvani O, Fang Y, Wang C, Foster LJ, Reiner NE. An exosome-based secretion pathway is responsible for protein export from Leishmania and communication with macrophages. J Cell Sci 2010; 123(6): 842-52. 67. Silverman JM, Clos J, Horakova E, Wang AY, Wiesgigl M, Kelly I, Lynn MA, McMaster WR, Foster LJ, Levings MK, Reiner NE. Leishmania exosomes modulate innate and adaptive immune responses through effects on monocytes and dendritic cells. J Immunol 2010; 185(9): 5011-22. 68. Sreekumar PG, Kannan R, Kitamura M, Spee C, Barron E, Ryan SJ, Hinton DR. αB crystallin is apically secreted within exosomes by polarized human retinal pigment epithelium and provides neuroprotection to adjacent cells. PLoS One 2010; 5(10): e12578. 69. Staubach S, Razawi H, Hanisch FG. Proteomics of MUC1-containing lipid rafts from plasma membranes and exosomes of human breast carcinoma cells MCF-7. Proteomics 2009; 9(10): 2820-35. 70. Stenmark H. Rab GTPases as coordinators of vesicle traffic. Nat Rev Mol Cell Biol 2009; 10: 513-25. 71. Thery C, Boussac M, Veron P, Ricciardi-Castagnoli P, Raposo G, Garin J, Amigorena S. Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles. J Immunol 2001; 166(12): 7309-18. 72.Trocoli Torrecilhas AC, Tonelli RR, Pavanelli WR, da Silva JS, Schumacher RI, de Souza W, E Silva NC, de Almeida Abrahamsohn I, Colli W, Manso Alves MJ. Trypanosoma cruzi: parasite shed vesicles increase heart parasitism and generate an intense inflammatory response. Microbes Infect 2009; 11(1): 29-39. 73. Twu O, de Miguel N, Lustig G, Stevens GC, Vashisht AA, Wohlschlegel JA, Johnson PJ. Trichomonas vaginalis exosomes deliver cargo to host cells and mediate host: Parasite interactions. PLoS Pathog 2013; 9(7): e1003482. 74.Twu O, Johnson PJ. Parasite extracellular vesicles: Mediators of intercellular communication. PLoS Pathog 2014; 10(8): e1004289. 75. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007; 9(6): 654-9. 76. Van der Goot FG, Gruenberg J. Intra-endosomal membrane traffic. Trends Cell Biol 2006; 16: 514-21. 77. Van Niel G, Porto-Carreiro I, Simoes S, Raposo G. Exosomes: A common pathway for a specialized function. J Biochem 2006; 140(1): 13-21. 78. Vidal M, Sainte-Marie J, Philippot JR, Bienvenue A. A symmetric distribution of phospholipids in the membrane of vesicles released during in vitro maturation of guinea pig reticulocytes: Evidence precluding a role for “aminophospholipidtranslocase”. J Cell Physiol 1989; 140(3): 455-62. 79. Vlassov AV, Magdaleno S, Setterquist R, Conrad R. Exosomes: Current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta 2012; 1820(7): 940-48. 80. Wubbolts R, Leckie RS, Veenhuizen PT, Schwarzmann G,Mobius W,Hoernschemeyer J, Slot JW, Geuze HJ, StoorvogelW. Proteomic and biochemical analyses of human B cell-derived exosomes. J Biol Chem 2003; 278(13): 10963-72. 81. Wurdinger T, Gatson NN, Balaj L, Kaur B, Breakefield XO, Pegtel DM. Extracellular vesicles and their convergence with viral pathways. Adv Virol 2012; Article ID: 767694. 82. Zhu H, Fan GC. Extracellular/circulating microRNAs and their potential role in cardiovascular disease. Am J Cardiovasc Dis 2011; 1(2): 138.