DOI QR코드

DOI QR Code

Glutamine and Leucine Provide Enhanced Protective Immunity Against Mucosal Infection with Herpes Simplex Virus Type 1

  • Uyangaa, Erdenebileg (College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University) ;
  • Lee, Hern-Ku (Department of Immunology, Chonbuk National University Medical School) ;
  • Eo, Seong Kug (College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University)
  • Received : 2012.08.29
  • Accepted : 2012.09.14
  • Published : 2012.10.31

Abstract

Besides their role as building blocks of protein, there are growing evidences that some amino acids have roles in regulating key metabolic pathways that are necessary for maintenance, growth, reproduction, and immunity. Here, we evaluated the modulatory functions of several amino acids in protective immunity against mucosal infection of herpes simplex virus type 1 (HSV-1). We found that glutamine (Gln) and leucine (Leu) showed enhanced protective immunity to HSV-1 mucosal infection when two administration of Gln and single administration of Leu per day, but not when administered in combinations. Ameliorated clinical signs of HSV-1 challenged mice by the intraperitoneal administration of Gln and Leu were closely associated with viral burden and IFN-${\gamma}$ production in the vaginal tract at 2 and 4 days post-infection. In addition, the enhanced production of vaginal IFN-${\gamma}$ appeared to be caused by NK and HSV-1 antigen-specific Th1-type CD4+ T cells recruited into vaginal tract of mice treated with Gln and Leu, which indicates that IFN-${\gamma}$, produced by NK and Th1-type CD4+ T cells, may be critical to control the outcome of diseases caused by HSV-1 mucosal infection. Collectively, our results indicate that intraperitoneal administration of Gln and Leu following HSV-1 mucosal infection could provide beneficial effects for the modulation of protective immunity, but dosage and frequency of administration should be carefully considered, because higher frequency and overdose of Gln and Leu, or their combined treatment, showed detrimental effects to protective immunity.

Keywords

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)

References

  1. Wu, G. 2009. Amino acids: metabolism, functions, and nutrition. Amino Acids 37: 1-17.
  2. Suenaga, R., S. Tomonaga, H. Yamane, I. Kurauchi, Y. Tsuneyoshi, H. Sato, D. M. Denbow, and M. Furuse. 2008. Intracerebroventricular injection of L-arginine induces sedative and hypnotic effects under an acute stress in neonatal chicks. Amino Acids 35: 139-146.
  3. Wu, G., F. W. Bazer, T. A. Davis, L. A. Jaeger, G. A. Johnson, S. W. Kim, D. A. Knabe, C. J. Meininger, T. E. Spencer, and Y. L. Yin. 2007. Important roles for the arginine family of amino acids in swine nutrition and production. Livest. Sci. 112: 8-22.
  4. Wu, G., F. W. Bazer, T. A. Cudd, W. S. Jobgen, S. W. Kim, A. Lassala, P. Li, J. H. Matis, C. J. Meininger, and T. E. Spencer. 2007. Pharmacokinetics and safety of arginine supplementation in animals. J. Nutr. 137(6 Suppl 2):1673S-1680S.
  5. Wu, G., J. K. Collins, P. Perkins-Veazie, M. Siddiq, K. D. Dolan, K. A. Kelly, C. L. Heaps, and C. J. Meininger. 2007. Dietary supplementation with watermelon pomace juice enhances arginine availability and ameliorates the metabolic syndrome in Zucker diabetic fatty rats. J. Nutr. 137: 2680-2685.
  6. Fu, W. J., T. E. Haynes, R. Kohli, J. Hu, W. Shi, T. E. Spencer, R. J. Carroll, C. J. Meininger, and G. Wu. 2005. Dietary L-arginine supplementation reduces fat mass in Zucker diabetic fatty rats. J. Nutr. 135: 714-721.
  7. Jobgen, W., W. J. Fu, H. Gao, P. Li, C. J. Meininger, S. B. Smith, T. E. Spencer, and G. Wu. 2009. High fat feeding and dietary L-arginine supplementation differentially regulate gene expression in rat white adipose tissue. Amino Acids 37: 187-198.
  8. Wang, J., L. Chen, P. Li, X. Li, H. Zhou, F. Wang, D. Li, Y. Yin, and G. Wu. 2008. Gene expression is altered in piglet small intestine by weaning and dietary glutamine supplementation. J. Nutr. 138: 1025-1032.
  9. Escobar, J., J. W. Frank, A. Suryawan, H. V. Nguyen, S. R. Kimball, L. S. Jefferson, and T. A. Davis. 2005. Physiological rise in plasma leucine stimulates muscle protein synthesis in neonatal pigs by enhancing translation initiation factor activation. Am. J. Physiol. Endocrinol. Metab. 288: E914-E921.
  10. Escobar, J., J. W. Frank, A. Suryawan, H. V. Nguyen, S. R. Kimball, L. S. Jefferson, and T. A. Davis. 2006. Regulation of cardiac and skeletal muscle protein synthesis by individual branched-chain amino acids in neonatal pigs. Am. J. Physiol. Endocrinol. Metab. 290: E612-E621.
  11. Meijer, A. J. and P. F. Dubbelhuis. 2004. Amino acid signalling and the integration of metabolism. Biochem. Biophys. Res. Commun. 313: 397-403.
  12. Yao, K., Y. L. Yin, W. Chu, Z. Liu, D. Deng, T. Li, R. Huang, J. Zhang, B. Tan, W. Wang, and G. Wu. 2008. Dietary arginine supplementation increases mTOR signaling activity in skeletal muscle of neonatal pigs. J. Nutr. 138: 867-872.
  13. Li, P., Y. L. Yin, D. Li, S. W. Kim, and G. Wu. 2007. Amino acids and immune function. Br. J. Nutr.98: 237-252.
  14. Tan, B., X. G. Li, X. Kong, R. Huang, Z. Ruan, K. Yao, Z. Deng, M. Xie, I. Shinzato, Y. Yin, and G. Wu. 2009. Dietary L-arginine supplementation enhances the immune status in early-weaned piglets. Amino Acids 37: 323-331.
  15. Van Brummelen, R. and D. du Toit. 2007. L-methionine asimmune supportive supplement: a clinical evaluation. Amino Acids 33: 157-163.
  16. Macchiarulo, A., E. Camaioni, R. Nuti, and R. Pellicciari. 2009. Highlights at the gate of tryptophan catabolism: a review on the mechanisms of activation and regulation of indoleamine 2,3-dioxygenase (IDO), a novel target in cancer disease. Amino Acids 37: 219-229.
  17. Platten, M., P. P. Ho, S. Youssef, P. Fontoura, H. Garren, E. M. Hur, R. Gupta, L. Y. Lee, B. A. Kidd, W. H. Robinson, R. A. Sobel, M. L. Selley, and L. Steinman. 2005. Treatment of autoimmune neuroinflammation with a synthetic tryptophan metabolite. Science 310: 850-855.
  18. Lacey, J. M. and D. W. Wilmore. 1990. Is glutamine a conditionally essential amino acid? Nutr. Rev. 48: 297-309.
  19. Roth, E., J. Funovics, F. Mühlbacher, M. Schemper, W. Mauritz, P. Sporn, and A. Fritsch. 1982. Metabolic disorders in severe abdominal sepsis: glutamine deficiency in skeletal muscle. Clin. Nutr. 1: 25-41.
  20. Gamrin, L., P. Essen, A. M. Forsberg, E. Hultman, and J. Wernerman. 1996. A descriptive study of skeletal muscle metabolism in critically ill patients: free amino acids, energy-rich phosphates, protein, nucleic acids, fat, water, and electrolytes. Crit. Care Med. 24: 575-583.
  21. Yeh, C. L., C. S. Hsu, S. L. Yeh, and W. J. Chen. 2005. Dietary glutamine supplementation modulates Th1/Th2 cytokine and interleukin-6 expressions in septic mice. Cytokine 31: 329-334.
  22. Peng, X., H. Yan, Z. You, P. Wang, and S. Wang. 2006. Glutamine granule-supplemented enteral nutrition maintains immunological function in severely burned patients. Burns 32: 589-593.
  23. Crawford, J. and H. J. Cohen. 1985. The essential role of L-glutamine in lymphocyte differentiation in vitro. J. Cell. Physiol. 124: 275-282.
  24. Newsholme, P. 2001. Why is L-glutamine metabolism important to cells of the immune system in health, postinjury, surgery or infection? J. Nutr. 131(9 Suppl): 2515S-2522S.
  25. Pithon-Curi, T. C., R. I. Schumacher, J. J. Freitas, C. Lagranha, P. Newsholme, A. C. Palanch, S. Q. Doi, and R. Curi. 2003. Glutamine delays spontaneous apoptosis in neutrophils. Am. J. Physiol. Cell. Physiol. 284: C1355-C1361.
  26. Chang, W. K., K. D. Yang, and M. F. Shaio. 1999. Effect of glutamine on Th1 and Th2 cytokine responses of human peripheral blood mononuclear cells. Clin. Immunol. 93: 294-301.
  27. Rohde, T., D. A. MacLean, and B. Klarlund Pedersen. 1996. Glutamine, lymphocyte proliferation and cytokine production. Scand. J. Immunol. 44: 648-650.
  28. Hörig, H., G. C. Spagnoli, L. Filgueira, R. Babst, H. Gallati, F. Harder, A. Juretic, and M. Heberer. 1993. Exogenous glutamine requirement is confined to late events of T cell activation. J. Cell. Biochem. 53: 343-351.
  29. Klimberg, V. S. and J. L. McClellan. 1996. Claude H. Organ, Jr. Honorary Lectureship. Glutamine, cancer, and its therapy. Am. J. Surg. 172: 418-424.
  30. Rohde, T., H. Ullum, J. P. Rasmussen, J. H. Kristensen, E. Newsholme, and B. K. Pedersen. 1995. Effects of glutamine on the immune system: influence of muscular exercise and HIV infection. J. Appl. Physiol. 79: 146-150.
  31. Lynch, C. J., B. J. Patson, J. Anthony, A. Vaval, L. S. Jefferson, and T. C. Vary. 2002. Leucine is a direct-acting nutrient signal that regulates protein synthesis in adipose tissue. Am. J. Physiol. Endocrinol. Metab. 283: E503-E513.
  32. Koelle, D. M. and L. Corey. 2008. Herpes simplex: insights on pathogenesis and possible vaccines. Annu. Rev. Med. 59: 381-395.
  33. Wilson, S. S., E. Fakioglu, and B. C. Herold. 2009. Novel approaches in fighting herpes simplex virus infections. Expert Rev. Anti Infect Ther. 7: 559-568.
  34. Eo, S. K., S. Lee, S. Chun, and B. T. Rouse. 2001. Modulation of immunity against herpes simplex virus infection via mucosal genetic transfer of plasmid DNA encoding chemokines. J. Virol. 75: 569-578.
  35. Frentsch, M., O. Arbach, D. Kirchhoff, B. Moewes, M. Worm, M. Rothe, A. Scheffold, and A. Thiel. 2005. Direct access to CD4+ T cells specific for defined antigens according to CD154 expression. Nat. Med. 11: 1118-1124.
  36. Sommer, M. H., M. H. Xavier, M. B. Fialho, C. M. Wannmacher, and M. Wajner. 1994. The influence of amino acids on mitogen-activated proliferation of human lymphocytes in vitro. Int. J. Immunopharmacol. 16: 865-872.
  37. Dobbs, M. E., J. E. Strasser, C. F. Chu, C. Chalk, and G. N. Milligan. 2005. Clearance of herpes simplex virus type 2 by CD8+ T cells requires gamma interferon and either perforin- or Fas-mediated cytolytic mechanisms. J. Virol. 79: 14546-14554.

Cited by

  1. Glutamine supplementation suppresses herpes simplex virus reactivation vol.127, pp.7, 2012, https://doi.org/10.1172/jci88990
  2. Novel metabolic and physiological functions of branched chain amino acids: a review vol.8, pp.1, 2012, https://doi.org/10.1186/s40104-016-0139-z
  3. Regulation of intestinal health by branched‐chain amino acids vol.89, pp.1, 2012, https://doi.org/10.1111/asj.12937
  4. Isoleucine Plays an Important Role for Maintaining Immune Function vol.20, pp.7, 2012, https://doi.org/10.2174/1389203720666190305163135
  5. Vitamin D, zinc and glutamine: Synergistic action with OncoTherad immunomodulator in interferon signaling and COVID-19 (Review) vol.47, pp.3, 2012, https://doi.org/10.3892/ijmm.2021.4844
  6. Virus Infections and Host Metabolism-Can We Manage the Interactions? vol.11, pp.None, 2012, https://doi.org/10.3389/fimmu.2020.594963
  7. Amino acid metabolism and signalling pathways: potential targets in the control of infection and immunity vol.11, pp.1, 2021, https://doi.org/10.1038/s41387-021-00164-1
  8. Amino acid metabolism and signalling pathways: potential targets in the control of infection and immunity vol.75, pp.9, 2021, https://doi.org/10.1038/s41430-021-00943-0
  9. PRACTICAL USE OF GOAT MILK AND COLOSTRUM vol.14, pp.5, 2012, https://doi.org/10.15407/biotech14.05.038