Parasites, Hosts and Diseases

The Korea Society for Parasitology and Tropical Medicine (대한기생충학·열대의학회)
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Parasitic Helminth Cystatin Inhibits DSS-Induced Intestinal Inflammation Via IL-$10^+F4/80^+$ Macrophage Recruitment

  • Jang, Sung-Won (Department of Parasitology, School of Medicine, Pusan National University) ;
  • Cho, Min-Kyoung (Department of Parasitology, School of Medicine, Pusan National University) ;
  • Park, Mi-Kyung (Department of Parasitology, School of Medicine, Pusan National University) ;
  • Kang, Shin-Ae (Department of Parasitology, School of Medicine, Pusan National University) ;
  • Na, Byoung-Kuk (Department of Parasitology, Institute of Health Sciences, Gyeongsang National University School of Medicine) ;
  • Ahn, Soon-Cheol (Department of Microbiology and 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 : 2011.06.05
  • Accepted : 2011.08.30
  • Published : 2011.09.30
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Abstract

Many immune down-regulatory molecules have been isolated from parasites, including cystatin (cystain protease inhibitor). In a previous study, we isolated and characterized Type I cystatin (CsStefin-1) of the liver fluke, Clonorchis sinensis. To investigate whether the CsStefin-1 might be a new host immune modulator, we induced intestinal inflammation in mice by dextran sodium sulfate (DSS) and treated them with recombinant CsStefin-1 (rCsStefin-1). The disease activity index (DAI) increased in DSS only-treated mice. In contrast, the DAI value was significantly reduced in rCsStefin-1-treated mice than DSS only-treated mice. In addition, the colon length of DSS only-treated mice was shorter than that of rCsStefin-1 treated mice. The secretion levels of IFN-${\gamma}$ and TNF-${\alpha}$ in the spleen and mesenteric lymph nodes (MLNs) were significantly increased by DSS treatment, but the level of TNF-${\alpha}$ in MLNs was significantly decreased by rCsStefin-1 treatment. IL-10 production in both spleen and MLNs was significantly increased, and IL-$10^+F4/80^+$ macrophage cells were significantly increased in the spleen and MLNs of rCsStefin-1 treated mice after DSS treatment. In conclusion, rCsStefin-1 could reduce the intestinal inflammation occurring after DSS treatment, these effects might be related with recruitment of IL-10 secreting macrophages.

Keywords

References

  1. Wang LJ, Cao Y, Shi HN. Helminth infections and intestinal inflammation. World J Gastroenterol 2008; 14: 5125-5132. https://doi.org/10.3748/wjg.14.5125
  2. Magen E, Borkow G, Bentwich Z, Mishal J, Scharf S. Can worms defend our hearts? Chronic helminthic infections may attenuate the development of cardiovascular diseases. Med Hypotheses 2005; 64: 904-909. https://doi.org/10.1016/j.mehy.2004.09.028
  3. Fleming JO, Cook TD. Multiple sclerosis and the hygiene hypothesis. Neurology 2006; 67: 2085-2086. https://doi.org/10.1212/01.wnl.0000247663.40297.2d
  4. Cooke A, Zaccone P, Raine T, Phillips JM, Dunne DW. Infection and autoimmunity: Are we winning the war, only to lose the peace? Trends Parasitol 2004; 20: 316-321. https://doi.org/10.1016/j.pt.2004.04.010
  5. Yang J, Zhao J, Yang Y, Zhang L, Yang X, Zhu X, Ji M, Sun N, Su C. Schistosoma japonicum egg antigens stimulate CD4 CD25 T cells and modulate airway inflammation in a murine model of asthma. Immunology 2007; 120: 8-18.
  6. Akiho H, Blennerhassett P, Deng Y, Collins SM. Role of IL-4, IL-13, and STAT6 in inflammation-induced hypercontractility of murine smooth muscle cells. Am J Physiol Gastrointest Liver Physiol 2002; 282: G226-232.
  7. Feillet H, Bach JF. Increased incidence of inflammatory bowel disease: The price of the decline of infectious burden? Curr Opin Gastroenterol 2004; 20: 560-564. https://doi.org/10.1097/00001574-200411000-00010
  8. Fiocchi C. Inflammatory bowel disease: Etiology and pathogenesis. Gastroenterology 1998; 115: 182-205. https://doi.org/10.1016/S0016-5085(98)70381-6
  9. Weinstock JV, Summers RW, Elliott DE. Role of helminths in regulating mucosal inflammation. Springer Semin Immunopathol 2005; 27: 249-271. https://doi.org/10.1007/s00281-005-0209-3
  10. Summers RW, Elliott DE, Urban JF Jr, Thompson R, Weinstock JV. Trichuris suis therapy in Crohn's disease. Gut 2005; 54: 87-90. https://doi.org/10.1136/gut.2004.041749
  11. Elliott DE, Urban JJ, Argo CK, Weinstock JV. Does the failure to acquire helminthic parasites predispose to Crohn's disease? Faseb J 2000; 14: 1848-1855. https://doi.org/10.1096/fj.99-0885hyp
  12. Reardon C, Sanchez A, Hogaboam CM, McKay DM. Tapeworm infection reduces epithelial ion transport abnormalities in murine dextran sulfate sodium-induced colitis. Infect Immun 2001; 69: 4417-4423. https://doi.org/10.1128/IAI.69.7.4417-4423.2001
  13. Khan WI, Blennerhasset PA, Varghese AK, Chowdhury SK, Omsted P, Deng Y, Collins SM. Intestinal nematode infection ameliorates experimental colitis in mice. Infect Immun 2002; 70: 5931-5937. https://doi.org/10.1128/IAI.70.11.5931-5937.2002
  14. Gregory WF, Blaxter ML, Maizels RM. Differentially expressed, abundant trans-spliced cDNAs from larval Brugia malayi. Mol Biochem Parasitol 1997; 87: 85-95. https://doi.org/10.1016/S0166-6851(97)00050-9
  15. Park SK, Cho MK, Park HK, Lee KH, Lee SJ, Choi SH, Ock MS, Jeong HJ, Lee MH, Yu HS. Macrophage migration inhibitory factor homologs of Anisakis simplex suppress Th2 response in allergic airway inflammation model via CD4+CD25+Foxp3+ T cell recruitment. J Immunol 2009; 182: 6907-6914. https://doi.org/10.4049/jimmunol.0803533
  16. Yenbutr P, Scott AL. Molecular cloning of a serine proteinase inhibitor from Brugia malayi. Infect Immun 1995; 63: 1745-1753.
  17. Murray J, Gregory WF, Gomez-Escobar N, Atmadja AK, Maizels RM. Expression and immune recognition of Brugia malayi VAL-1, a homologue of vespid venom allergens and Ancylostoma secreted proteins. Mol Biochem Parasitol 2001; 118: 89-96. https://doi.org/10.1016/S0166-6851(01)00374-7
  18. Vray B, Hartmann S, Hoebeke J. Immunomodulatory properties of cystatins. Cell Mol Life Sci 2002; 59: 1503-1512. https://doi.org/10.1007/s00018-002-8525-4
  19. Zavasnik-Bergant T, Repnik U, Schweiger A, Romih R, Jeras M, Turk V, Kos J. Differentiation- and maturation-dependent content, localization, and secretion of cystatin C in human dendritic cells. J Leukoc Biol 2005; 78: 122-134. https://doi.org/10.1189/jlb.0804451
  20. Chapman HA Jr, Reilly JJ Jr, Yee R, Grubb A. Identification of cystatin C, a cysteine proteinase inhibitor, as a major secretory product of human alveolar macrophages in vitro. Am Rev Respir Dis 1990; 141: 698-705. https://doi.org/10.1164/ajrccm/141.3.698
  21. Murray J, Manoury B, Balic A, Watts C, Maizels RM. Bm-CPI-2, a cystatin from Brugia malayi nematode parasites, differs from Caenorhabditis elegans cystatins in a specific site mediating inhibition of the antigen-processing enzyme AEP. Mol Biochem Parasitol 2005; 139: 197-203. https://doi.org/10.1016/j.molbiopara.2004.11.008
  22. Manoury B, Gregory WF, Maizels RM, Watts C. Bm-CPI-2, a cystatin homolog secreted by the filarial parasite Brugia malayi, in hibits class II MHC-restricted antigen processing. Curr Biol 2001; 11: 447-451. https://doi.org/10.1016/S0960-9822(01)00118-X
  23. Schonemeyer A, Lucius R, Sonnenburg B, Brattig N, Sabat R, Schilling K, Bradley J, Hartmann S. Modulation of human T cell responses and macrophage functions by onchocystatin, a secreted protein of the filarial nematode Onchocerca volvulus. J Immunol 2001; 167: 3207-3215.
  24. Klotz C, Ziegler T, Figueiredo AS, Rausch S, Hepworth MR, Obsivac N, Sers C, Lang R, Hammerstein P, Lucius R, Hartmann S. A helminth immunomodulator exploits host signaling events to regulate cytokine production in macrophages. PLoS Pathog 2011; 7: e1001248. https://doi.org/10.1371/journal.ppat.1001248
  25. Schnoeller C, Rausch S, Pillai S, Avagyan A, Wittig BM, Loddenkemper C, Hamann A, Hamelmann E, Lucius R, Hartmann S. A helminth immunomodulator reduces allergic and inflammatory responses by induction of IL-10-producing macrophages. J Immunol 2008; 180: 4265-4272.
  26. Tarasuk M, Vichasri Grams S, Viyanant V, Grams R. Type I cystatin (stefin) is a major component of Fasciola gigantica excretion/secretion product. Mol Biochem Parasitol 2009; 167: 60-71. https://doi.org/10.1016/j.molbiopara.2009.04.010
  27. Kang JM, Lee KH, Sohn WM, Na BK. Identification and functional characterization of CsStefin-1, a cysteine protease inhibitor of Clonorchis sinensis. Mol Biochem Parasitol 2011; 177: 126-134. https://doi.org/10.1016/j.molbiopara.2011.02.010
  28. Jeong YI, Kim SH, Ju JW, Cho SH, Lee WJ, Park JW, Park YM, Lee SE. Clonorchis sinensis-derived total protein attenuates airway inflammation in murine asthma model by inducing regulatory T cells and modulating dendritic cell functions. Biochem Biophys Res Commun 2011; 407: 793-800. https://doi.org/10.1016/j.bbrc.2011.03.102
  29. Kim JY, Cho MK, Choi SH, Lee KH, Ahn SC, Kim DH, Yu HS. Inhibition of dextran sulfate sodium (DSS)-induced intestinal inflammation via enhanced IL-10 and TGF-beta production by galectin-9 homologues isolated from intestinal parasites. Mol Biochem Parasitol 2010; 174: 53-61. https://doi.org/10.1016/j.molbiopara.2010.06.014
  30. van Meeteren ME, van Bergeijk JD, van Dijk AP, Tak CJ, Meijssen MA, Zijlstra FJ. Intestinal permeability and contractility in murine colitis. Mediators Inflamm 1998; 7: 163-168. https://doi.org/10.1080/09629359891090
  31. Kamada N, Hisamatsu T, Okamoto S, Chinen H, Kobayashi T, Sato T, Sakuraba A, Kitazume MT, Sugita A, Koganei K, Akagawa KS, Hibi T. Unique CD14 intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-gamma axis. J Clin Invest 2008; 118: 2269-2280.
  32. Rogler G, Hausmann M, Vogl D, Aschenbrenner E, Andus T, Falk W, Andreesen R, Scholmerich J, Gross V. Isolation and phenotypic characterization of colonic macrophages. Clin Exp Immunol 1998; 112: 205-215. https://doi.org/10.1046/j.1365-2249.1998.00557.x
  33. Vitorino R, Lobo MJ, Ferrer-Correira AJ, Dubin JR, Tomer KB, Domingues PM, Amado FM. Identification of human whole saliva protein components using proteomics. Proteomics 2004; 4: 1109-1115. https://doi.org/10.1002/pmic.200300638
  34. Di Quinzio MK, Oliva K, Holdsworth SJ, Ayhan M, Walker SP, Rice GE, Georgiou HM, Permezel M. Proteomic analysis and characterisation of human cervico-vaginal fluid proteins. Aust N Z J Obstet Gynaecol 2007; 47: 9-15. https://doi.org/10.1111/j.1479-828X.2006.00671.x
  35. Manoury B, Hewitt EW, Morrice N, Dando PM, Barrett AJ, Watts C. An asparaginyl endopeptidase processes a microbial antigen for class II MHC presentation. Nature 1998; 396: 695-699. https://doi.org/10.1038/25379
  36. Owczarek D, Cibor D, Szczepanek M, Mach T. Biological therapy of inflammatory bowel disease. Pol Arch Med Wewn 2009; 119: 84-88.
  37. Fiorino G, Cesarini M, Danese S. Biological therapy for ulcerative colitis: What is after anti-TNF. Curr Drug Targets 2011; 12: 1433-1439. https://doi.org/10.2174/138945011796818225
  38. Hoentjen F, van Bodegraven AA. Safety of anti-tumor necrosis factor therapy in inflammatory bowel disease. World J Gastroenterol 2009; 15: 2067-2073. https://doi.org/10.3748/wjg.15.2067
  39. Stallmach A, Hagel S, Bruns T. Adverse effects of biologics used for treating IBD. Best Pract Res Clin Gastroenterol 2010; 24: 167-182. https://doi.org/10.1016/j.bpg.2010.01.002
  40. Akbari O, DeKruyff RH, Umetsu DT. Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Nat Immunol 2001; 2: 725-731. https://doi.org/10.1038/90667
  41. Saraiva M, O'Garra A. The regulation of IL-10 production by immune cells. Nat Rev Immunol 2010; 10: 170-181. https://doi.org/10.1038/nri2711
  42. Presser K, Schwinge D, Wegmann M, Huber S, Schmitt S, Quaas A, Maxeiner JH, Finotto S, Lohse AW, Blessing M, Schramm C. Coexpression of TGF-beta1 and IL-10 enables regulatory T cells to completely suppress airway hyperreactivity. J Immunol 2008; 181: 7751-7758.
  43. Mottet C, Uhlig HH, Powrie F. Cutting edge: Cure of colitis by CD4+CD25+ regulatory T cells. J Immunol 2003; 170: 3939-3943.

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