Skip to main content

Advertisement

Log in

Exosome-like vesicles derived by Schistosoma japonicum adult worms mediates M1 type immune- activity of macrophage

  • Original Paper
  • Published:
Parasitology Research Aims and scope Submit manuscript

Abstract

Exosomes are 30–100-nm membrane vesicles of endocytic origin that are released into the extracellular space upon fusion of the multi-vesicular bodies (MVB) with the plasma membrane, while initial studies described that the role of exosomes was a reticulocyte cargo-disposal mechanism allowing remodeling of the plasma membrane during the maturation of reticulocytes to erythrocytes. Recent studies indicate that exosomes are secreted by most cells and pathogens and play an important role in intercellular signaling and exert regulatory function by carrying bioactive molecules. As numerous pathogens, adult worm of Schistosoma japonicum (S. japonicum) reside in mesenteric veins of definitive host including man and mammal animals. It was reported that the worms or the eggs also have specialized secretion systems to export effector proteins or other molecules into host target cells. However, the mechanisms involved remained unclear. This study investigated the isolation of the exosome-like vesicles secreted by S. japonicum adult worms and its immune activity on microphage in vitro. In this report, we identified exosome-based secretion as a new mechanism for protein secretion by S. japonicum. Electron microscopy tomography revealed the previously unidentified ultrastructural detail of exosome-like vesicles with high resolution; they were found to be typical spherical shape and to have a diverse population that varies in size of 30–100 nm. Exosome-like vesicles isolated from S. japonicum contained a significantly different protein compared with debris pelleted and the apoptosis body. We also demonstrate that macrophages were preferentially differentiated into the M1 subtype while being treated with S. japonicum exosome-like vesicles. This study reveals there are exosome-like vesicles derived by S. japonicum adult worms, and the exosome-like vesicles can mediate M1-type immune- activity of macrophage.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Ahmed SF, Oswald IP, Caspar P, Hieny S, Keefer L, Sher A, James SL (1997) Developmental differences determine larval susceptibility to nitric oxide-mediated killing in a murine model of vaccination against Schistosoma mansoni. Infect Immun 65(1):219–226

    PubMed Central  CAS  PubMed  Google Scholar 

  • Baietti MF, Zhang Z, Mortier E, Melchior A, Degeest G, Geeraerts A, Ivarsson Y, Depoortere F, Coomans C, Vermeiren E, Zimmermann P, David G (2012) Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat Cell Biol 14(7):677–685

    Article  CAS  PubMed  Google Scholar 

  • Barron L, Wynn TA (2011) Macrophage activation governs schistosomiasis-induced inflammation and fibrosis. Eur J Immunol 41(9):2509–2514

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bhatnagar S, Shinagawa K, Castellino FJ, Schorey JS (2007) Exosomes released from macrophages infected with intracellular pathogens stimulate a proinflammatory response in vitro and in vivo. Blood 110(9):3234–3244

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bronte V, Zanovello P (2005) Regulation of immune responses by L-arginine metabolism. Nat Rev Immunol 5(8):641–654

    Article  CAS  PubMed  Google Scholar 

  • Colley DG, Bustinduy AL, Secor WE, King CH (2014) Human schistosomiasis. Lancet 383(9936):2253–2264

    Article  PubMed  Google Scholar 

  • Doenhoff MJ, Cioli D, Utzinger J (2008) Praziquantel: mechanisms of action, resistance and new derivatives for schistosomiasis. Curr Opin Infect Dis 21(6):659–667

    Article  CAS  PubMed  Google Scholar 

  • Gehrmann U, Qazi KR, Johansson C, Hultenby K, Karlsson M, Lundeberg L, Gabrielsson S, Scheynius A (2011) Nanovesicles from Malassezia sympodialis and host exosomes induce cytokine responses—novel mechanisms for host-microbe interactions in atopic eczema. PLoS One 6(7):e21480

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gordon S (2007) Macrophage heterogeneity and tissue lipids. J Clin Invest 11(1):89–93

    Google Scholar 

  • Greenspoon PB, M’Gonigle LK (2014) Host-parasite interactions and the evolution of non-random mating. Evolution

  • Hesse M, Modolell M, La Flamme AC, Schito M, Fuentes JM, Cheever AW, Pearce EJ, Wynn TA (2001) Differential regulation of nitric oxide synthase-2 and arginase-1 by type 1/type 2 cytokines in vivo: granulomatous pathology is shaped by the pattern of L-arginine metabolism. J Immunol 167(11):6533–6544

    Article  CAS  PubMed  Google Scholar 

  • Jia TW, Zhou XN, Wang XH, Utzinger J, Steinmann P, Wu XH (2007) Assessment of the age-specific disability weight of chronic schistosomiasis japonica. Bull World Health Organ 85(6):458–465

    Article  PubMed Central  PubMed  Google Scholar 

  • Johnstone RM, Adam M, Hammond JR, Orr L, Turbide C (1987) Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem 262(19):9412–9420

    CAS  PubMed  Google Scholar 

  • King CH (2010) Parasites and poverty: the case of schistosomiasis. Acta Trop 113(2):95–104

    Article  PubMed Central  PubMed  Google Scholar 

  • Krausgruber T, Blazek K, Smallie T, Alzabin S, Lockstone H, Sahgal N, Hussell T, Feldmann M, Udalova IA (2011) IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nat Immunol 12(3):231–238

    Article  CAS  PubMed  Google Scholar 

  • Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227(5259):680–685

    Article  CAS  PubMed  Google Scholar 

  • Lasser C, Eldh M, Lotvall J (2012) Isolation and characterization of RNA-containing exosomes. J Vis Exp 59:e3037

    PubMed  Google Scholar 

  • Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M (2004) The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 25(12):677–686

    Article  CAS  PubMed  Google Scholar 

  • Marcilla A, Toledo R, Bernal D, Trelis M, Cortés A, Sotillo CF, Minguez MT, Valero ML, Sánchez Del Pino MM, Mu Oz-Antoli C (2012) Extracellular vesicles from parasitic helminths contain specific excretory/secretory proteins and are internalized in intestinal host cells. PLoS One 7(9):e45974

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Martin-Jaular L, Nakayasu ES, Ferrer M, Almeida IC, Del Portillo HA (2011) Exosomes from Plasmodium yoelii-infected reticulocytes protect mice from lethal infections. PLoS One 6:e26588

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mathivanan S, Ji H, Simpson RJ (2010) Exosomes: extracellular organelles important in intercellular communication. J Proteomics 73(10):1907–1920

    Article  CAS  PubMed  Google Scholar 

  • Meckes DJ, Raab-Traub N (2011) Microvesicles and viral infection. J Virol 85(24):12844–12854

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Nickel W (2010) Pathways of unconventional protein secretion. Curr Opin Biotechnol 21(5):621–626

    Article  CAS  PubMed  Google Scholar 

  • Peng J, Yang Y, Feng X, Cheng G, Lin J (2010) Molecular characterizations of an inhibitor of apoptosis from Schistosoma japonicum. Parasitol Res 106(4):967–976

    Article  PubMed  Google Scholar 

  • Podolska M, Nadolna K (2014) Acetylcholinesterase secreted by Anisakis simplex larvae (Nematoda: Anisakidae) parasitizing herring, Clupea harengus: an inverse relationship of enzyme activity in the host-parasite system. Parasitol Res 113(6):2231–2238

    Article  PubMed Central  PubMed  Google Scholar 

  • Regev-Rudzki N, Hill AF, Baum J, Cowman AF, Wilson DW, Carvalho TG, Coleman BM, Rug M, Bursac D, Angrisano F, Gee M (2013) Cell-cell communication between malaria-infected red blood cells via exosome-like vesicles. Cell 153(5):1120

    Article  CAS  PubMed  Google Scholar 

  • Satoh T, Takeuchi O, Vandenbon A, Yasuda K, Tanaka Y, Kumagai Y, Miyake T, Matsushita K, Okazaki T, Saitoh T, Honma K, Matsuyama T, Yui K, Tsujimura T, Standley DM, Nakanishi K, Nakai K, Akira S (2010) The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection. Nat Immunol 11(10):936–944

    Article  CAS  PubMed  Google Scholar 

  • Schorey JS, Bhatnagar S (2008) Exosome function: from tumor immunology to pathogen biology. Traffic 9(6):871–881

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sica A, Mantovani A (2012) Macrophage plasticity and polarization: in vivo veritas. J Clin Invest 122(3):787–795

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Silverman JM, Reiner NE (2011) Exosomes and other microvesicles in infection biology: organelles with unanticipated phenotypes. Cell Microbiol 13(1):1–9

    Article  CAS  PubMed  Google Scholar 

  • Silverman JM, Clos J, Horakova E, Wang AY, Wiesgigl M, Kelly I, Lynn MA, McMaster WR, Foster LJ, Levings MK, Reiner NE (2010) Leishmania exosomes modulate innate and adaptive immune responses through effects on monocytes and dendritic cells. J Immunol 185(9):5011–5022

    Article  CAS  PubMed  Google Scholar 

  • Simpson RJ, Lim JW, Moritz RL, Mathivanan S (2009) Exosomes: proteomic insights and diagnostic potential. Expert Rev Proteomics 6(3):267–283

    Article  CAS  PubMed  Google Scholar 

  • Twu O, de Miguel N, Lustig G, Stevens GC, Vashisht AA, Wohlschlegel JA, Johnson PJ (2013) Trichomonas vaginalis exosomes deliver cargo to host cells and mediate host:parasite interactions. PLoS Pathog 9(7):e1003482

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, Shibuya K, Salomon JA, Abdalla S, Aboyans V (2012) Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the global burden of disease study 2010. Lancet 380(9859):2163–2196

    Article  PubMed  Google Scholar 

  • Wang W, Li HJ, Qu GL, Xing YT, Yang ZK, Dai JR, Liang YS (2014) Is there a reduced sensitivity of dihydroartemisinin against praziquantel-resistant Schistosoma japonicum? Parasitol Res 113(1):223–228

    Article  CAS  PubMed  Google Scholar 

  • Wu W, Huang Y (2013) Application of praziquantel in schistosomiasis japonica control strategies in China. Parasitol Res 112(3):909–915

    Article  PubMed  Google Scholar 

  • Yang X, Liu J, Yue Y, Chen W, Song M, Zhan X, Wu Z (2014) Cloning, expression and characterisation of a type II cystatin from Schistosoma japonicum, which could regulate macrophage activation. Parasitol Res 113(11):3985–3992

    Article  PubMed  Google Scholar 

  • Zhou XN, Wang LY, Chen MG, Wu XH, Jiang QW, Chen XY, Zheng J, Utzinger J (2005) The public health significance and control of schistosomiasis in China—then and now. Acta Trop 72:145–1478

    Google Scholar 

  • Zhou XN, Bergquist R, Leonardo L, Yang GJ, Yang K, Sudomo M, Olveda R (2010) Schistosomiasis japonica control and research needs. Adv Parasitol 96(2–3):97–105

    Google Scholar 

  • Zhu J, Xu Z, Chen X, Zhou S, Zhang W, Chi Y, Li W, Song X, Liu F, Su C (2014) Parasitic antigens alter macrophage polarization during Schistosoma japonicum infection in mice. Parasitol Vector 7:122

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81201309 and 30972574) and a grant from the China Postdoctoral Science Foundation (No. 2011M501363), the Natural Science Foundation of Guangdong Province, China (No. S2012040007256), and Foundation of Doctoral Program of Higher Education of China (No.20120171120049).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Xi Sun or Zhongdao Wu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, L., Li, Z., Shen, J. et al. Exosome-like vesicles derived by Schistosoma japonicum adult worms mediates M1 type immune- activity of macrophage. Parasitol Res 114, 1865–1873 (2015). https://doi.org/10.1007/s00436-015-4373-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-015-4373-7

Keywords

Navigation