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Protease-Activated Receptor 2 Is Involved in Th2 Responses against Trichinella spiralis Infection

  • Park, Mi-Kyung (Department of Parasitology, School of Medicine, Pusan National University) ;
  • Cho, Min-Kyoung (Department of Parasitology, School of Medicine, Pusan National University) ;
  • Kang, Shin-Ae (Department of Parasitology, School of Medicine, Pusan National University) ;
  • Park, Hye-Kyung (Department of Internal Medicine, School of Medicine, Pusan National University) ;
  • Kim, Yun-Seong (Department of Internal Medicine, School of Medicine, Pusan National University) ;
  • Kim, Ki-Uk (Department of Internal Medicine, School of Medicine, Pusan National University) ;
  • Ahn, Soon-Cheol (Department of Mcirobiology & Immunology, School of Medicine, Pusan National University) ;
  • Kim, Dong-Hee (Department of Nursing, College of Nursing, Pusan National University) ;
  • Yu, Hak-Sun (Department of Parasitology, School of Medicine, Pusan National University)
  • Received : 2011.04.25
  • Accepted : 2011.06.21
  • Published : 2011.09.30

Abstract

In order to get a better understanding of the role of protease-activated receptor 2 (PAR2) in type 2 helper T (Th2) cell responses against Trichinella spiralis infection, we analyzed Th2 responses in T. spiralis-infected PAR2 knockout (KO) mice. The levels of the Th2 cell-secreted cytokines, IL-4, IL-5, and IL-13 were markedly reduced in the PAR2 KO mice as compared to the wild type mice following infection with T. spiralis. The serum levels of parasite-specific IgE increased significantly in the wild type mice as the result of T. spiralis infection, but this level was not significantly increased in PAR2 KO mice. The expression level of thymic stromal lymphopoietin, IL-25, and eotaxin gene (the genes were recently known as Th2 response initiators) of mouse intestinal epithelial cells were increased as the result of treatment with T. spiralis excretory-secretory proteins. However, the expression of these chemokine genes was inhibited by protease inhibitor treatments. In conclusion, PAR2 might involve in Th2 responses against T. spiralis infection.

Keywords

References

  1. Devlin MG, Gasser RB, Cocks TM. Initial support for the hypothesis that PAR2 is involved in the immune response to Nippostrongylus brasiliensis in mice. Parasitol Res 2007; 101: 105-109.
  2. Kapsenberg ML. Dendritic-cell control of pathogen-driven T-cell polarization. Nat Rev Immunol 2003; 3: 984-993. https://doi.org/10.1038/nri1246
  3. McKerrow JH, Caffrey C, Kelly B, Loke P, Sajid M. Proteases in parasitic diseases. Annu Rev Pathol 2006; 1: 497-536. https://doi.org/10.1146/annurev.pathol.1.110304.100151
  4. Ghaemmaghami AM, Gough L, Sewell HF, Shakib F. The proteolytic activity of the major dust mite allergen Der p 1 conditions dendritic cells to produce less interleukin-12: allergen-induced Th2 bias determined at the dendritic cell level. Clin Exp Allergy 2002; 32: 1468-1475. https://doi.org/10.1046/j.1365-2745.2002.01504.x
  5. Tovey ER, Chapman MD, Platts-Mills TA. Mite faeces are a major source of house dust allergens. Nature 1981; 289: 592-593. https://doi.org/10.1038/289592a0
  6. Rosario NA. Total IgE in respiratory allergies and infections by intestinal parasites. J Pediatr (Rio J) 2007; 83: 92-93; author reply 93-94.
  7. Traynelis SF, Trejo J. Protease-activated receptor signaling: New roles and regulatory mechanisms. Curr Opin Hematol 2007; 14: 230-235. https://doi.org/10.1097/MOH.0b013e3280dce568
  8. Ossovskaya VS, Bunnett NW. Protease-activated receptors: Contribution to physiology and disease. Physiol Rev 2004; 84: 579-621. https://doi.org/10.1152/physrev.00028.2003
  9. Holzhausen M, Spolidorio LC, Vergnolle N. Role of protease-activated receptor-2 in inflammation, and its possible implications as a putative mediator of periodontitis. Mem Inst Oswaldo Cruz 2005; 100 (suppl 1): 177-180.
  10. Fabre MV, Beiting DP, Bliss SK, Appleton JA. Immunity to Trichinella spiralis muscle infection. Vet Parasitol 2009; 159: 245-248. https://doi.org/10.1016/j.vetpar.2008.10.051
  11. Cwiklinski K, Meskill D, Robinson MW, Pozio E, Appleton JA, Connolly B. Cloning and analysis of a Trichinella pseudospiralis muscle larva secreted serine protease gene. Vet Parasitol 2009; 159: 268-271. https://doi.org/10.1016/j.vetpar.2008.10.036
  12. Liu MY, Wang XL, Fu BQ, Li CY, Wu XP, Le Rhun D, Chen QJ, Boireau P. Identification of stage-specifically expressed genes of Trichinella spiralis by suppression subtractive hybridization. Parasitology 2007; 134: 1443-1455. https://doi.org/10.1017/S0031182007002855
  13. Park HK, Chang SW, Kang SW, Cho MK, Choi SH, Hong YC, Lee YS, Jeong HJ, Yu HS. Expressed sequence tags of Trichinella spiralis muscle stage larvae. Korean J Parasitol 2008; 46: 59-63. https://doi.org/10.3347/kjp.2008.46.2.59
  14. Dixon H, Blanchard C, Deschoolmeester ML, Yuill NC, Christie JW, Rothenberg ME, Else KJ. The role of Th2 cytokines, chemokines and parasite products in eosinophil recruitment to the gastrointestinal mucosa during helminth infection. Eur J Immunol 2006; 36: 1753-1763. https://doi.org/10.1002/eji.200535492
  15. Diaz A, Allen JE. Mapping immune response profiles: The emerging scenario from helminth immunology. Eur J Immunol 2007; 37: 3319-3326. https://doi.org/10.1002/eji.200737765
  16. Goodridge HS, Marshall FA, Else KJ, Houston KM, Egan C, Al-Riyami L, Liew FY, Harnett W, Harnett MM. Immunomodulation via novel use of TLR4 by the filarial nematode phosphorylcholine-containing secreted product, ES-62. J Immunol 2005; 174: 284-293.
  17. Thomas PG, Carter MR, Atochina O, Da'Dara AA, Piskorska D, McGuire E, Harn DA. Maturation of dendritic cell 2 phenotype by a helminth glycan uses a Toll-like receptor 4-dependent mechanism. J Immunol 2003; 171: 5837-5841.
  18. Aksoy E, Zouain CS, Vanhoutte F, Fontaine J, Pavelka N, Thieblemont N, Willems F, Ricciardi-Castagnoli P, Goldman M, Capron M, Ryffel B, Trottein F. Double-stranded RNAs from the helminth parasite Schistosoma activate TLR3 in dendritic cells. J Biol Chem 2005; 280: 277-283.
  19. Lee KE, Kim JW, Jeong KY, Kim KE, Yong TS, Sohn MH. Regulation of German cockroach extract-induced IL-8 expression in human airway epithelial cells. Clin Exp Allergy 2007; 37: 1364-1373. https://doi.org/10.1111/j.1365-2222.2007.02797.x
  20. Buddenkotte J, Stroh C, Engels IH, Moormann C, Shpacovitch VM, Seeliger S, Vergnolle N, Vestweber D, Luger TA, Schulze-Osthoff K, Steinhoff M. Agonists of proteinase-activated receptor-2 stimulate upregulation of intercellular cell adhesion molecule-1 in primary human keratinocytes via activation of NF-kappa B. J Invest Dermatol 2005; 124: 38-45. https://doi.org/10.1111/j.0022-202X.2004.23539.x
  21. Hurst SD, Muchamuel T, Gorman DM, Gilbert JM, Clifford T, Kwan S, Menon S, Seymour B, Jackson C, Kung TT, Brieland JK, Zurawski SM, Chapman RW, Zurawski G, Coffman RL. New IL-17 family members promote Th1 or Th2 responses in the lung: In vivo function of the novel cytokine IL-25. J Immunol 2002; 169: 443-453.
  22. Fort MM, Cheung J, Yen D, Li J, Zurawski SM, Lo S, Menon S, Clifford T, Hunte B, Lesley R, Muchamuel T, Hurst SD, Zurawski G, Leach MW, Gorman DM, Rennick DM. IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo. Immunity 2001; 15: 985-995. https://doi.org/10.1016/S1074-7613(01)00243-6
  23. Angkasekwinai P, Park H, Wang YH, Wang YH, Chang SH, Corry DB, Liu YJ, Zhu Z, Dong C. Interleukin 25 promotes the initiation of proallergic type 2 responses. J Exp Med 2007; 204: 1509-1517. https://doi.org/10.1084/jem.20061675
  24. Ikeda K, Nakajima H, Suzuki K, Kagami S, Hirose K, Suto A, Saito Y, Iwamoto I. Mast cells produce interleukin-25 upon Fc epsilon RI-mediated activation. Blood 2003; 101: 3594-3596. https://doi.org/10.1182/blood-2002-09-2817
  25. Ballantyne SJ, Barlow JL, Jolin HE, Nath P, Williams AS, Chung KF, Sturton G, Wong SH, McKenzie AN. Blocking IL-25 prevents airway hyperresponsiveness in allergic asthma. J Allergy Clin Immunol 2007; 120: 1324-1331. https://doi.org/10.1016/j.jaci.2007.07.051
  26. Al-Shami A, Spolski R, Kelly J, Keane-Myers A, Leonard WJ. A role for TSLP in the development of inflammation in an asthma model. J Exp Med 2005; 202: 829-839. https://doi.org/10.1084/jem.20050199
  27. Miyata M, Hatsushika K, Ando T, Shimokawa N, Ohnuma Y, Katoh R, Suto H, Ogawa H, Masuyama K, Nakao A. Mast cell regulation of epithelial TSLP expression plays an important role in the development of allergic rhinitis. Eur J Immunol 2008; 38: 1487-1492. https://doi.org/10.1002/eji.200737809
  28. Omori M, Ziegler S. Induction of IL-4 expression in CD4(+) T cells by thymic stromal lymphopoietin. J Immunol 2007; 178: 1396-1404.
  29. Kouzaki H, O'Grady SM, Lawrence CB, Kita H. Proteases induce production of thymic stromal lymphopoietin by airway epithelial cells through protease-activated receptor-2. J Immunol 2009; 183:1427-1434. https://doi.org/10.4049/jimmunol.0900904

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