Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

The characteristics of NK cells in Schistosoma japonicum-infected mouse spleens

Abstract

Natural killer (NK) cells are classic innate immune cells that play roles in many types of infectious disease. Recently, some new characteristics of NK cells were discovered. In this study, C57BL/6 mice were infected with Schistosoma japonicum for 5–6 weeks and lymphocytes were isolated from the spleen to detect some of the NK cell characteristics by multiparametric flow cytometry. The results revealed that the S. japonicum infection induced a large amount of NK cells, although the percentage of NK cells was not increased significantly. At the same time, the results showed that infected mouse splenic NK cells expressed increased levels of CD25 and CD69 and produced more IL-2, IL-4, and IL-17 and less IFN-γ after stimulation with PMA and ionomycin. This meant that NK cells played a role in S. japonicum infection. Moreover, decreased NKG2A/C/E (CD94) expression levels were detected on the surface of NK cells from infected mouse spleens, which might serve as a NK cell activation mechanism. Additionally, high levels of IL-10, but not PD-1, were expressed on the infected mouse NK cells, which implied that functional exhaustion might exist in the splenic NK cells from S. japonicum-infected mice. Collectively, our results suggest that NK cells play important roles in the course of S. japonicum infection.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  1. Addison EG, North J, Bakhsh I, Marden C, Haq S, Al-Sarraj S, Malayeri R, Wickremasinghe RG, Davies JK, Lowdell MW (2005) Ligation of CD8alpha on human natural killer cells prevents activation-induced apoptosis and enhances cytolytic activity. Immunology 116:354–361

  2. Bengsch B, Martin B, Thimme R (2014) Restoration of HBV-specific CD8+ T cell function by PD-1 blockade in inactive carrier patients is linked to T cell differentiation. J Hepatol 61:1212–1219

  3. Bernstein HB, Plasterer MC, Schiff SE, Kitchen CM, Kitchen S, Zack JA (2006) CD4 expression on activated NK cells: ligation of CD4 induces cytokine expression and cell migration. J Immunol 177:3669–3676

  4. Bernstein HB, Wang G, Plasterer MC, Zack JA, Ramasastry P, Mumenthaler SM, Kitchen CM (2009) CD4+ NK cells can be productively infected with HIV, leading to downregulation of CD4 expression and changes in function. Virology 387:59–66

  5. Blackburn SD, Wherry EJ (2007) IL-10, T cell exhaustion and viral persistence. Trends Microbiol 15:143–146

  6. Chen AL, Qiu XY, Wang W, Zhou CL, Zeng X, Liu XJ, Qiu JF, Wang Y (2014) The quantitative and functional changes of NK cells in mice infected with Angiostrongylus cantonensis. Parasitol Res 113:2087–2094

  7. Chen D, Luo X, Xie H, Gao Z, Fang H, Huang J (2013) Characteristics of IL-17 induction by Schistosoma japonicum infection in C57BL/6 mouse liver. Immunology 139:523–532

  8. Cua DJ, Tato CM (2010) Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol 10:479–489

  9. Dunphy SE, Guinan KJ, Chorcora CN, Jayaraman J, Traherne JA, Trowsdale J, Pende D, Middleton D, Gardiner CM (2015) 2DL1, 2DL2 and 2DL3 all contribute to KIR phenotype variability on human NK cells. Genes Immun 16:301–310

  10. Gunturi A, Berg RE, Forman J (2004) The role of CD94/NKG2 in innate and adaptive immunity. Immunol Res 30:29–34

  11. Hofer E, Sobanov Y, Brostjan C, Lehrach H, Duchler M (2001) The centromeric part of the human natural killer (NK) receptor complex: lectin-like receptor genes expressed in NK, dendritic and endothelial cells. Immunol Rev 181:5–19

  12. Hoffmann KF, Cheever AW, Wynn TA (2000) IL-10 and the dangers of immune polarization: excessive type 1 and type 2 cytokine responses induce distinct forms of lethal immunopathology in murine schistosomiasis. J Immunol 164:6406–6416

  13. Hou X, Zhou R, Wei H, Sun R, Tian Z (2009) NKG2D-retinoic acid early inducible-1 recognition between natural killer cells and Kupffer cells in a novel murine natural killer cell-dependent fulminant hepatitis. Hepatology 49:940–949

  14. Hou X, Yu F, Man S, Huang D, Zhang Y, Liu M, Ren C, Shen J (2012) Negative regulation of Schistosoma japonicum egg-induced liver fibrosis by natural killer cells. PLoS Negl Trop Dis 6, e1456

  15. Kwilasz AJ, Grace PM, Serbedzija P, Maier SF, Watkins LR (2014) The therapeutic potential of interleukin-10 in neuroimmune diseases. Neuropharmacology 96:55–69

  16. Lanier LL (2003) Natural killer cell receptor signaling. Curr Opin Immunol 15:308–314

  17. Lanier LL (2008) Up on the tightrope: natural killer cell activation and inhibition. Nat Immunol 9:495–502

  18. Licona-Limon P, Henao-Mejia J, Temann AU, Gagliani N, Licona-Limon I, Ishigame H, Hao L, Herbert DR, Flavell RA (2013) Th9 cells drive host immunity against gastrointestinal worm infection. Immunity 39:744–757

  19. Luo X, Xie H, Chen D, Yu X, Wu F, Li L, Wu C, Huang J (2014) Changes in NK and NKT cells in mesenteric lymph nodes after a Schistosoma japonicum infection. Parasitol Res 113:1001–1009

  20. McManus DP, Gray DJ, Li Y, Feng Z, Williams GM, Stewart D, Rey-Ladino J, Ross AG (2010) Schistosomiasis in the People’s Republic of China: the era of the Three Gorges Dam. Clin Microbiol Rev 23:442–466

  21. O’Sullivan TE, Sun JC (2015) Generation of natural killer cell memory during viral infection. J Innate Immun. doi: 10.1159/000375494

  22. Pandya AD, Al-Jaderi Z, Hoglund RA, Holmoy T, Harbo HF, Norgauer J, Maghazachi AA (2011) Identification of human NK17/NK1 cells. PLoS One 6, e26780

  23. Raczkowski F, Ritter J, Heesch K, Schumacher V, Guralnik A, Hocker L, Raifer H, Klein M, Bopp T, Harb H, Kesper DA, Pfefferle PI, Grusdat M, Lang PA, Mittrucker HW, Huber M (2013) The transcription factor interferon regulatory factor 4 is required for the generation of protective effector CD8+ T cells. Proc Natl Acad Sci U S A 110:15019–15024

  24. Rodrigues V, Cordeiro-da-Silva A, Laforge M, Ouaissi A, Akharid K, Silvestre R, Estaquier J (2014) Impairment of T cell function in parasitic infections. PLoS Negl Trop Dis 8, e2567

  25. Saunders M, Taubert A, Dafa'Alla T, Zahner H (2008) Effect of chemotherapeutic treatment on cytokine (IFN-gamma, IL-2, IL-4, IL-5, IL-10) gene transcription in response to specific antigens in Brugia malayi-infected Mastomys coucha. Parasitol Res 103:1163–1176

  26. Singh A, Dey AB, Mohan A, Mitra DK (2014) Programmed death-1 receptor suppresses gamma-IFN producing NKT cells in human tuberculosis. Tuberculosis (Edinb) 94:197–206

  27. Smyth MJ, Hayakawa Y, Takeda K, Yagita H (2002) New aspects of natural-killer-cell surveillance and therapy of cancer. Nat Rev Cancer 2:850–861

  28. Sun H, Sun C, Xiao W (2014) Expression regulation of co-inhibitory molecules on human natural killer cells in response to cytokine stimulations. Cytokine 65:33–41

  29. Sun R, Gao B (2004) Negative regulation of liver regeneration by innate immunity (natural killer cells/interferon-gamma). Gastroenterology 127:1525–1539

  30. Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S (2008) Functions of natural killer cells. Nat Immunol 9:503–510

  31. Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, Yokoyama WM, Ugolini S (2011) Innate or adaptive immunity? The example of natural killer cells. Science 331:44–49

  32. Weaver CT, Hatton RD, Mangan PR, Harrington LE (2007) IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol 25:821–852

  33. Wherry EJ (2011) T cell exhaustion. Nat Immunol 12:492–499

  34. Wilson MS, Mentink-Kane MM, Pesce JT, Ramalingam TR, Thompson R, Wynn TA (2007) Immunopathology of schistosomiasis. Immunol Cell Biol 85:148–154

  35. Xie H, Chen D, Luo X, Gao Z, Fang H, Huang J (2013) Some characteristics of IL-5-producing T cells in mouse liver induced by Schistosoma japonicum infection. Parasitol Res 112:1945–1951

  36. Zafirova B, Wensveen FM, Gulin M, Polic B (2011) Regulation of immune cell function and differentiation by the NKG2D receptor. Cell Mol Life Sci 68:3519–3529

  37. Zhou H, Sun X, Lv Z, Shen Y, Peng H, Yang L, Zheng H, Fung MC, Cao J, Wu Z (2012) The secretions products from invading cercariae of S. japonicum (0-3hRP) restrain mouse dendritic cells to mature. Parasitol Res 110:119–126

Download references

Acknowledgments

This work was supported by a grant that was obtained from the College Scientific Research Projects in Guangzhou City (2012C117).

Author information

Correspondence to Nuo Dong or Jun Huang.

Additional information

Lu Li, Hefei Cha and Xiuxue Yu contributed equally to this work.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Li, L., Cha, H., Yu, X. et al. The characteristics of NK cells in Schistosoma japonicum-infected mouse spleens. Parasitol Res 114, 4371–4379 (2015). https://doi.org/10.1007/s00436-015-4674-x

Download citation

Keywords

  • Schistosoma japonicum
  • Spleen
  • NK cell