Folia Parasitologica, vol. 64 (2017)

Folia Parasitologica 64:029 (2017) | 10.14411/fp.2017.029

Echinococcus multilocularis vesicular fluid inhibits activation and proliferation of natural killer cells

Anne-Pauline Bellanger1,2, Valentine Mougey1, Jean-René Pallandre3, Houssein Gbaguidi-Haore4, Yann Godet3, Laurence Millon1,2
1 Parasitology-Mycology Department, University Hospital, Besançon, France;
2 Chrono-Environnement CNRS 6249 Research Team, Franche-Comté University, Besançon, France;
3 INSERM Unit 1098, University of Franche-Comté, Besançon, France;
4 Infection Control Department, Besançon University Hospital, Besançon, France

Alveolar echinococcosis is a severe chronic helminthic disease that mimics slow-growing liver cancer. The immune evasion strategy of Echinococcus multilocularis Leuckart, 1863 remains poorly understood. The aim of this study was to investigate in vitro the impact of E. multilocularis vesicular fluid (Em-VF) on peripheral blood mononuclear cells (PBMC) and on natural killer (NK) cells. PBMC and NK cells were exposed to Em-VF (1 µg/ml) during six days. The effect of Em-VF was assessed on CD69, viability and proliferation, and on and transforming growth factor β (TGF-β), interferon γ (IFN-γ), interleukin 17 (IL-17) and interleukin 10, using flow cytometry and ELISA, respectively. Exposure to Em-VF had no bearing on PBMC's viability, proliferation and expression of CD69. In contrast, higher levels of IL-17 at day three and of TGF-β at day six were observed in PBMC supernatant after exposure to Em-VF (p < 0.05, Wilcoxon signed-rank test). Exposure to Em-VF induced a significant decrease of CD69 expression of NK cells at day three and a significant decrease of proliferation of NK cells at day six (p < 0.05, Wilcoxon signed-rank test). In contrast, NK cells viability and levels of cytokines did not vary significantly over Em-VF stimulation. Exposure to Em-VF had a significant bearing on activation and proliferation of NK cells. NK cells may play an important role in the immune response of the host against E. multilocularis.

Keywords: NK cells, alveolar echinococcosis, immune response, CD69

Received: March 3, 2017; Accepted: August 5, 2017; Published online: August 25, 2017


References

  1. Azad A., Yin Lim S., D'Costa Z., Jones K., Diana A., Sansom O.J., Kruger P., Liu S., McKenna W.G., Dushek O., Muschel R.J., Fokas E. 2017: PD-L1 blockade enhances response of pancreatic ductal adenocarcinoma to radiotherapy. EMBO Mol. Med. 9: 167-180. Go to original source... Go to PubMed...
  2. Bellanger A.P., Pallandre J.R., Gbaguidi-Haore H., Knapp J., Malézieux N., Lignon T., Borg C., Millon L. 2015: Investigating the impact of Echinococcus multilocularis vesicular fluid on human cells from healthy blood donors. J. Immunol. Methods 417: 52-59. Go to original source... Go to PubMed...
  3. Borrego F., Robertson M.J., Ritz J., Peña J., Solana R. 1999: CD69 is a stimulatory receptor for natural killer cell and its cytotoxic effect is blocked by CD94 inhibitory receptor. Immunology 97: 159-165. Go to original source... Go to PubMed...
  4. Gottstein B., Soboslay P., Ortona E., Wang J., Siracusano A., Vuitton D.Α. 2017: Immunology of alveolar and cystic echinococcosis (AE and CE). Adv. Parasitol. 96: 1-54. Go to original source... Go to PubMed...
  5. Iannello A., Thompson T.W., Ardolino M., Marcus A., Raulet D.H. 2016: Immunosurveillance and immunotherapy of tumors by innate immune cells. Curr. Opin. Immunol. 38: 52-58. Go to original source... Go to PubMed...
  6. Jerud, E.S., Bricard G., Porcelli S.A. 2006: Natural killer T cells: roles in tumor immunosurveillance and tolerance. Transfus. Med. Hemother. 33: 18-36. Go to original source... Go to PubMed...
  7. Margos M.C., Grandgirard D., Leib S., Gottstein B. 2011: In vitro induction of lymph node cell proliferation by mouse bone marrow dendritic cells following stimulation with different Echinococcus multilocularis antigens. J. Helminthol. 85: 128-137. Go to original source... Go to PubMed...
  8. Mejri N., Müller J., Gottstein B. 2011: Intraperitoneal murine Echinococcus multilocularis infection induces differentiation of TGF-β-expressing DCs that remain immature. Parasite Immunol. 33: 471-482. Go to original source... Go to PubMed...
  9. Moretta L., Pietra G., Vacca P., Pende D., Moretta F., Bertaina A., Mingari M.C., Locatelli F., Moretta A. 2016: Human NK cells: From surface receptors to clinical applications. Immunol Lett. 178: 15-19. Go to original source... Go to PubMed...
  10. Muenst S., Läubli H., Soysal S.D., Zippelius A., Tzankov A., Hoeller S. 2016: The immune system and cancer evasion strategies: therapeutic concepts. J. Intern. Med. 279: 541-562. Go to original source... Go to PubMed...
  11. Nono J.K., Pletinckx K., Lutz M.B., Brehm K. 2012: Excretory/secretory-products of Echinococcus multilocularis larvae induce apoptosis and tolerogenic properties in dendritic cells in vitro. PLoS Negl. Trop. Dis. 6: e1516. Go to original source... Go to PubMed...
  12. Vivier E., Raulet D.H., Moretta A., Caligiuri M.A., Zitvogel L., Lanier L.L., Yokoyama W.M., Ugolini, S. 2011: Innate or adaptive immunity? The example of natural killer cells. Science 331: 44-49. Go to original source... Go to PubMed...
  13. Vuitton D.A., Bresson-Hadni S., Laroche L., Kaiserlian D., Guerret-Stocker S., Bresson J.L., Gillet M. 1989: Cellular immune response in Echinococcus multilocularis infection in humans. II. Natural killer cell activity and cell subpopulations in the blood and in the periparasitic granuloma of patients with alveolar echinococcosis. Clin. Exp. Immunol. 78: 67-74. Go to PubMed...
  14. Vuitton D.A., Zhang S.L., Yang Y., Godot V., Beurton I., Mantion G., Bresson-Hadni S. 2006: Survival strategy of Echinococcus multilocularis in the human host. Parasitol. Int. 55: S51-S55. Go to original source... Go to PubMed...
  15. Wang J., Gottstein B. 2016: Immunoregulation in larval Echinococcus multilocularis infection. Parasite Immunol. 38: 182-192. Go to original source... Go to PubMed...
  16. Wang J., Lin R., Zhang W., Li L., Gottstein B., Blagosklonov O., Lü G., Zhang C., Lu X., Vuitton D.A., Wen H. 2014: Transcriptional profiles of cytokine/chemokine factors of immune cell-homing to the parasitic lesions: a comprehensive one-year course study in the liver of E. multilocularis-infected mice. PLoS ONE 9: e91638. Go to original source... Go to PubMed...
  17. Zhang S., Hüe S., Sène D., Penfornis A., Bresson-Hadni S., Kantelip B., Caillat-Zucman S., Vuitton D.A. 2008: Expression of major histocompatibility complex class I chain-related molecule A, NKG2D, and transforming growth factor-beta in the liver of humans with alveolar echinococcosis: new actors in the tolerance to parasites? J. Infect. Dis. 197: 1341-1349. Go to original source... Go to PubMed...