IMMUNE NETWORK

The Korean Association of Immunobiologists (대한면역학회)
권호 표지
DOI QR코드

DOI QR Code

Anti-herpes Activity of Vinegar-processed Daphne genkwa Flos Via Enhancement of Natural Killer Cell Activity

  • Uyangaa, Erdenebileg (College of Veterinary Medicine and Bio-Safety Research Institute, Specialized Campus, Chonbuk National University) ;
  • Choi, Jin Young (College of Veterinary Medicine and Bio-Safety Research Institute, Specialized Campus, Chonbuk National University) ;
  • Ryu, Hyung Won (Natural Medicine Research Center, KRIBB) ;
  • Oh, Sei-Ryang (Natural Medicine Research Center, KRIBB) ;
  • Eo, Seong Kug (College of Veterinary Medicine and Bio-Safety Research Institute, Specialized Campus, Chonbuk National University)
  • Received : 2015.01.13
  • Accepted : 2015.03.25
  • Published : 2015.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Herpes simplex virus (HSV) is a common causative agent of genital ulceration and can lead to subsequent neurological disease in some cases. Here, using a genital infection model, we tested the efficacy of vinegar-processed flos of Daphne genkwa (vp-genkwa) to modulate vaginal inflammation caused by HSV-1 infection. Our data revealed that treatment with optimal doses of vp-genkwa after, but not before, HSV-1 infection provided enhanced resistance against HSV-1 infection, as corroborated by reduced mortality and clinical signs. Consistent with these results, treatment with vp-genkwa after HSV-1 infection reduced viral replication in the vaginal tract. Furthermore, somewhat intriguingly, treatment of vp-genkwa after HSV-1 infection increased the frequency and absolute number of $CD3^-NK1.1^+NKp46^+$ natural killer (NK) cells producing interferon (IFN)-${\gamma}$ and granyzme B, which indicates that vp-genkwa treatment induces the activation of NK cells. Supportively, secreted IFN-${\gamma}$ was detected at an increased level in vaginal lavages of mice treated with vp-genkwa after HSV-1 infection. These results indicate that enhanced resistance to HSV-1 infection by treatment with vp-genkwa is associated with NK cell activation. Therefore, our data provide a valuable insight into the use of vp-genkwa to control clinical severity in HSV infection through NK cell activation.

Keywords

References

  1. Shahin, V., W. Hafezi, H. Oberleithner, Y. Ludwig, B. Windoffer, H. Schillers, and J. E. Kuhn. 2006. The genome of HSV-1 translocates through the nuclear pore as a condensed rod-like structure. J. Cell Sci. 119: 23-30. https://doi.org/10.1242/jcs.02705
  2. Daniels, D., and S. Mortlock. 2008. Mixed HSV-1 and HSV-2 infection in a patient attending a GUM clinic. Br. J. Biomed. Sci. 65: 203-204. https://doi.org/10.1080/09674845.2008.11978131
  3. Pereira, V. S., R. N. Moizeis, T. A. Fernandes, J. M. Araujo, R. V. Meissner, and J. V. Fernandes. 2012. Herpes simplex virus type 1 is the main cause of genital herpes in women of Natal, Brazil. Eur. J. Obstet. Gynecol. Reprod. Biol. 161: 190-193.
  4. Lee, A. J. and A. A. Ashkar. 2012. Herpes simplex virus-2 in the genital mucosa: insights into the mucosal host response and vaccine development. Curr. Opin. Infect. Dis. 25: 92-99. https://doi.org/10.1097/QCO.0b013e32834e9a56
  5. Chentoufi, A.A., and L. Benmohamed. 2012. Mucosal herpes immunity and immunopathology to ocular and genital herpes simplex virus infections. Clin. Dev. Immunol. 2012: 149135.
  6. Grinde, B. 2013. Herpesviruses: latency and reactivation - viral strategies and host response. J. Oral Microbiol. 5: 22766. https://doi.org/10.3402/jom.v5i0.22766
  7. Auvert, B., R. Ballard, C. Campbell, M. Carael, M. Carton, G. Fehler, E. Gouws, C. MacPhail, D. Taljaard, D. J. Van, and B. Williams. 2001. HIV infection among youth in a South African mining town is associated with herpes simplex virus-2 seropositivity and sexual behaviour. AIDS 15: 885-898. https://doi.org/10.1097/00002030-200105040-00009
  8. Mugo, N., S. S. Dadabhai, R. Bunnell, J. Williamson, E. Bennett, I. Baya, N. Akinyi, I. Mohamed, and R. Kaiser. 2011. Prevalence of herpes simplex virus type 2 infection, human immunodeficiency virus/herpes simplex virus type 2 coinfection, and associated risk factors in a national, population- based survey in Kenya. Sex Transm. Dis. 38: 1059-1066. https://doi.org/10.1097/OLQ.0b013e31822e60b6
  9. Freeman, E. E., H. A. Weiss, J. R. Glynn, P. L. Cross, J. A. Whitworth, and R. J. Hayes. 2006. Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS 20: 73-83. https://doi.org/10.1097/01.aids.0000198081.09337.a7
  10. Parr, M. B., L. Kepple, M. R. McDermott, M. D. Drew, J. J. Bozzola, and E. L. Parr. 1994. A mouse model for studies of mucosal immunity to vaginal infection by herpes simplex virus type 2. Lab. Invest. 70: 369-380.
  11. Uyangaa, E., A. M. Patil, and S. K. Eo. 2014. Prophylactic and therapeutic modulation of innate and adaptive immunity against mucosal infection of herpes simplex virus. Immune Netw. 14: 187-200. https://doi.org/10.4110/in.2014.14.4.187
  12. Gill, N., K. L. Rosenthal, and A. A. Ashkar. 2005. NK and NKT cell-independent contribution of interleukin-15 to innate protection against mucosal viral infection. J. Virol. 79: 4470-4478. https://doi.org/10.1128/JVI.79.7.4470-4478.2005
  13. Harandi, A. M., B. Svennerholm, J. Holmgren, and K. Eriksson. 2001. Differential roles of B cells and IFN-${\gamma}$-secreting $CD4^+$ T cells in innate and adaptive immune control of genital herpes simplex virus type 2 infection in mice. J. Gen. Virol. 82: 845-853. https://doi.org/10.1099/0022-1317-82-4-845
  14. Milligan, G. N., and D. I. Bernstein. 1997. Interferon-gamma enhances resolution of herpes simplex virus type 2 infection of the murine genital tract. Virology 229: 259-268. https://doi.org/10.1006/viro.1997.8441
  15. Parr, M. B., and E. L. Parr. 1999. The role of gamma interferon in immune resistance to vaginal infection by herpes simplex virus type 2 in mice. Virology 258: 282-294. https://doi.org/10.1006/viro.1999.9739
  16. Harandi, A. M., B. Svennerholm, J. Holmgren, and K. Eriksson. 2001. Interleukin-12 (IL-12) and IL-18 are important in innate defense against genital herpes simplex virus type 2 infection in mice but are not required for the development of acquired gamma interferon-mediated protective immunity. J. Virol. 75: 6705-6709. https://doi.org/10.1128/JVI.75.14.6705-6709.2001
  17. Conrady, C. D., H. Jones, M. Zheng, and D. J. Carr. 2011. A functional type I interferon pathway drives resistance to cornea herpes simplex virus type 1 infection by recruitment of leukocytes. J. Biomed. Res. 25: 111-119. https://doi.org/10.1016/S1674-8301(11)60014-6
  18. Conrady, C. D., M. Zheng, N. A. Mandal, R. N. van, and D. J. Carr. 2013. IFN-${\alpha}$-driven CCL2 production recruits inflammatory monocytes to infection site in mice. Mucosal Immunol. 6: 45-55. https://doi.org/10.1038/mi.2012.46
  19. Hansen, M. L., A. Woetmann, T. Krejsgaard, K. L. Kopp, R. Sokilde, T. Litman, P. T. Straten, C. Geisler, M. A. Wasik, N. Odum, and K. W. Eriksen. 2011. IFN-${\alpha}$ primes T- and NK-cells for IL-15-mediated signaling and cytotoxicity. Mol. Immunol. 48: 2087-2093. https://doi.org/10.1016/j.molimm.2011.07.008
  20. Beuneu, H., J. Deguine, I. Bouvier, J. P. Di Santo, M. L. Albert, and P. Bousso. 2011. Cutting Edge: A dual role for type I IFNs during polyinosinic-polycytidylic acid-induced NK cell activation. J. Immunol. 187: 2084-2088. https://doi.org/10.4049/jimmunol.1004210
  21. Baranek, T., T. P. Manh, Y. Alexandre, M. A. Maqbool, J. Z. Cabeza, E. Tomasello, K. Crozat, G. Bessou, N. Zucchini, S. H. Robbins, E. Vivier, U. Kalinke, P. Ferrier, and M. Dalod. 2012. Differential responses of immune cells to type I interferon contribute to host resistance to viral infection. Cell Host Microbe 12: 571-584. https://doi.org/10.1016/j.chom.2012.09.002
  22. Kovalova, A., M. Ledvina, D. Saman, D. Zyka, M. Kubickova, L. Zidek, V. Sklenar, P. Pompach, D. Kavan, J. Bily, O. Vanek, Z. Kubinkova, M. Libigerova, L. Ivanova, M. Antolikova, H. Mrazek, D. Rozbesky, K. Hofbauerova, V. Kren, and K. Bezouska. 2010. Synthetic N-acetyl-D-glucosamine based fully branched tetrasaccharide, a mimetic of the endogenous ligand for CD69, activates $CD69^+$ killer lymphocytes upon dimerization via a hydrophilic flexible linker. J. Med. Chem. 53: 4050-4065. https://doi.org/10.1021/jm100055b
  23. Nielsen, C. H., P. Balachandran, O. Christensen, N. D. Pugh, H. Tamta, K. J. Sufka, X. Wu, A. Walsted, M. Schjorring-Thyssen, C. Enevold, and D. S. Pasco. 2010. Enhancement of natural killer cell activity in healthy subjects by Immulina$^{(R)}$, a Spirulina extract enriched for Braun-type lipoproteins. Planta Med. 76: 1802-1808. https://doi.org/10.1055/s-0030-1250043
  24. Jiangsu New Medical College. 1985. The Encyclopedia of Traditional Chinese medicine, 2nd ed. Shanghai Science and Technology, Shanghai. p. 2573-2574.
  25. Zhan, Z. J., C. Q. Fan, J. Ding, and J. M. Yue. 2005. Novel diterpenoids with potent inhibitory activity against endothelium cell HMEC and cytotoxic activities from a well-known TCM plant Daphne genkwa. Bioorg. Med. Chem. 13: 645-655. https://doi.org/10.1016/j.bmc.2004.10.054
  26. Li, H. S., and M. L. Xiao. 2012. Research progress of the Shi-Zao-Tang to treat malignant pleural effusion and ascites. Res. Integr. Tradit. Chin. West Med. 4: 93-94.
  27. Zheng, W., X. Gao, Q. Gu, C. Chen, Z. Wei, and F. Shi. 2007. Antitumor activity of daphnodorins from Daphne genkwa roots. Int. Immunopharmacol. 7: 128-134. https://doi.org/10.1016/j.intimp.2006.07.011
  28. Park, B. Y., B. S. Min, S. R. Oh, J. H. Kim, K. H. Bae, and H. K. Lee. 2006. Isolation of flavonoids, a biscoumarin and an amide from the flower buds of Daphne genkwa and the evaluation of their anti-complement activity. Phytother. Res. 20: 610-613. https://doi.org/10.1002/ptr.1915
  29. Uyangaa, E., J. Y. Choi, A. M. Patil, J. H. Kim, S. B. Kim, K. Kim, H. W. Ryu, S. R. Oh, and S. K. Eo. 2015. Functional restoration of exhausted $CD4^+$ and $CD8^+$ T cells in chronic viral infection by vinegar-processed flos of Daphne genkwa. Comp. Immunol. Microbiol. Infect. Dis. 39: 25-37. https://doi.org/10.1016/j.cimid.2015.02.001
  30. Geng, L., H. Sun, Y. Yuan, Z. Liu, Y. Cui, K. Bi, and X. Chen. 2013. Discrimination of raw and vinegar-processed Genkwa Flos using metabolomics coupled with multivariate data analysis: a discrimination study with metabolomics coupled with PCA. Fitoterapia 84: 286-294. https://doi.org/10.1016/j.fitote.2012.12.003
  31. Uyangaa, E., H. K. Lee, and S. K. Eo. 2012. Glutamine and leucine provide enhanced protective immunity against mucosal infection with herpes simplex virus type 1. Immune Netw. 12: 196-206. https://doi.org/10.4110/in.2012.12.5.196
  32. Lanier, L. L. 2008. Evolutionary struggles between NK cells and viruses. Nat. Rev. Immunol. 8: 259-268. https://doi.org/10.1038/nri2276
  33. Ferlazzo, G., and C. Munz. 2004. NK cell compartments and their activation by dendritic cells. J. Immunol. 172: 1333-1339. https://doi.org/10.4049/jimmunol.172.3.1333
  34. Zhang, Y., Y. Zhang, W. Gu, and B. Sun. 2014. TH1/TH2 cell differentiation and molecular signals. Adv. Exp. Med. Biol. 841: 15-44. https://doi.org/10.1007/978-94-017-9487-9_2
  35. Kang, H. B., K. S. Ahn, S. R. Oh, and J. W. Kim. 2014. Genkwadaphnin induces IFN-gamma via PKD1/NF-${\kappa}$B/STAT1 dependent pathway in NK-92 cells. PLoS One 9: e115146. https://doi.org/10.1371/journal.pone.0115146
  36. dib-Conquy, M., D. Scott-Algara, J. M. Cavaillon, and F. Souza-Fonseca-Guimaraes. 2014. TLR-mediated activation of NK cells and their role in bacterial/viral immune responses in mammals. Immunol. Cell Biol. 92: 256-262.
  37. Millard, A. L., R. Spirig, N. J. Mueller, J. D. Seebach, and R. Rieben. 2010. Inhibition of direct and indirect TLR-mediated activation of human NK cells by low molecular weight dextran sulfate. Mol. Immunol. 47: 2349-2358. https://doi.org/10.1016/j.molimm.2010.05.284
  38. Chen, S., G. Lin, L. Lei, X. You, C. Wu, W. Xu, M. Huang, L. Luo, Z. Wang, Y. Li, X. Zhao, and F. Yan. 2013. Hyperlipidemia modifies innate immune responses to lipopolysaccharide via the TLR-NF-${\kappa}$B signaling pathway. Inflammation 36: 968-976. https://doi.org/10.1007/s10753-013-9628-9
  39. Langers, I., V. Renoux, A. Reschner, A. Touze, P. Coursaget, J. Boniver, J. Koch, P. Delvenne, and N. Jacobs. 2014. Natural killer and dendritic cells collaborate in the immune response induced by the vaccine against uterine cervical cancer. Eur. J. Immunol. 44: 3585-3595. https://doi.org/10.1002/eji.201444594

Cited by

  1. Dual TLR2/9 Recognition of Herpes Simplex Virus Infection Is Required for Recruitment and Activation of Monocytes and NK Cells and Restriction of Viral Dissemination to the Central Nervous System vol.9, pp.None, 2015, https://doi.org/10.3389/fimmu.2018.00905
  2. Molecular Mechanisms Involved in Oxidative Stress-Associated Liver Injury Induced by Chinese Herbal Medicine: An Experimental Evidence-Based Literature Review and Network Pharmacology Study vol.19, pp.9, 2015, https://doi.org/10.3390/ijms19092745
  3. Wound Healing and the Use of Medicinal Plants vol.2019, pp.None, 2015, https://doi.org/10.1155/2019/2684108