DOI QR코드

DOI QR Code

Trichinella spiralis Infection Suppressed Gut Inflammation with $CD4^+CD25^+Foxp3^+$ T Cell Recruitment

  • Cho, Min Kyoung (Department of Parasitology, Pusan National University School of Medicine) ;
  • Park, Mi Kyung (Department of Parasitology, Pusan National University School of Medicine) ;
  • Kang, Shin Ae (Department of Parasitology, Pusan National University School of Medicine) ;
  • Choi, Seon Hee (Department of Parasitology, Pusan National University School of Medicine) ;
  • Ahn, Soon Cheol (Department of Microbiology and Immunology, Pusan National University School of Medicine) ;
  • Yu, Hak Sun (Department of Parasitology, Pusan National University School of Medicine)
  • 투고 : 2012.06.01
  • 심사 : 2012.08.02
  • 발행 : 2012.12.17

초록

In order to know the effect of pre-existing Trichinella spiralis infection on experimentally induced intestinal inflammation and immune responses, we induced colitis in T. spiralis-infected mice and observed the severity of colitis and the levels of Th1, Th2, and regulatory cytokines and recruitment of $CD4^+CD25^+Foxp3^+$ T (regulatory T; $T_{reg}$) cells. Female C57BL/6 mice were infected with 250 muscle larvae; after 4 weeks, induction of experimental colitis was performed using 3% dextran sulfate sodium (DSS). During the induction period, we observed severity of colitis, including weight loss and status of stool, and evaluated the disease activity index (DAI). A significantly low DAI and degree of weight loss were observed in infected mice, compared with uninfected mice. In addition, colon length in infected mice was not contracted, compared with uninfected mice. We also observed a significant increase in production of pro-inflammatory cytokines, IL-6 and IFN-${\gamma}$, in spleen lymphocytes treated with DSS; however, such an increase was not observed in infected mice treated with DSS. Of particular interest, production of regulatory cytokines, IL-10 and transforming growth factor (TGF)-${\beta}$, in spleen lymphocytes showed a significant increase in mice infected with T. spiralis. A similar result was observed in mesenteric lymph nodes (MLN). Subsets of the population of $T_{reg}$ cells in MLN and spleen showed significant increases in mice infected with T. spiralis. In conclusion, T. spiralis infection can inhibit the DSS-induced colitis in mice by enhancing the regulatory cytokine and $T_{reg}$ cells recruitment.

키워드

참고문헌

  1. Motomura Y, Wang H, Deng Y, El-Sharkawy RT, Verdu EF, Khan WI. Helminth antigen-based strategy to ameliorate inflammation in an experimental model of colitis. Clin Exp Immunol 2009; 155: 88-95. https://doi.org/10.1111/j.1365-2249.2008.03805.x
  2. Podolsky DK. Inflammatory bowel disease. N Engl J Med 2002; 347: 417-429. https://doi.org/10.1056/NEJMra020831
  3. Moreels TG, Pelckmans PA. The hygiene hypothesis and inflammatory bowel diseases: role of helminths. Acta Gastroenterol Belg 2006; 69: 413-417.
  4. Fiocchi C. Inflammatory bowel disease: Etiology and pathogenesis. Gastroenterology 1998; 115: 182-205. https://doi.org/10.1016/S0016-5085(98)70381-6
  5. 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
  6. Ruyssers NE, De Winter BY, De Man JG, Loukas A, Herman AG, Pelckmans PA, Moreels TG. Worms and the treatment of inflammatory bowel disease: Are molecules the answer? Clin Dev Immunol 2008; 2008: 567314.
  7. 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
  8. Summers RW, Elliott DE, Qadir K, Urban JF Jr, Thompson R, Weinstock JV. Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease. Am J Gastroenterol 2003; 98: 2034-2041. https://doi.org/10.1111/j.1572-0241.2003.07660.x
  9. Jasmer DP. Trichinella spiralis infected skeletal muscle cells arrest in G2/M and cease muscle gene expression. J Cell Biol 1993; 121: 785-793. https://doi.org/10.1083/jcb.121.4.785
  10. Despommier D, Aron L, Turgeon L. Trichinella spiralis: Growth of the intracellular (muscle) larva. Exp Parasitol 1975; 37: 108-116. https://doi.org/10.1016/0014-4894(75)90058-2
  11. Park HK, Cho MK, Choi SH, Kim YS, Yu HS. Trichinella spiralis: Infection reduces airway allergic inflammation in mice. Exp Parasitol 2011; 127: 539-544. https://doi.org/10.1016/j.exppara.2010.10.004
  12. Wirtz S, Neurath MF. Mouse models of inflammatory bowel disease. Adv Drug Deliv Rev 2007; 59: 1073-1083. https://doi.org/10.1016/j.addr.2007.07.003
  13. Wirtz S, Neufert C, Weigmann B, Neurath MF. Chemically induced mouse models of intestinal inflammation. Nat Protoc 2007; 2: 541-546. https://doi.org/10.1038/nprot.2007.41
  14. Perše M, Cerar A. Dextran sodium sulphate colitis mouse model: traps and tricks. J Biomed Biotechnol 2012; 2012: 718617.
  15. Yan Y, Kolachala V, Dalmasso G, Nguyen H, Laroui H, Sitaraman SV, Merlin D. Temporal and spatial analysis of clinical and molecular parameters in dextran sodium sulfate induced colitis. PLoS One 2009; 4: e6073. https://doi.org/10.1371/journal.pone.0006073
  16. Kang SA, Cho MK, Park MK, Kim DH, Hong YC, Lee YS, Cha HJ, Ock MS, Yu HS. Alteration of helper T-cell related cytokine production in splenocytes during Trichinella spiralis infection. Vet Parasitol 2012; 186: 319-327. https://doi.org/10.1016/j.vetpar.2011.12.002
  17. 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 2011; 174: 53-61.
  18. Nishitani Y, Tanoue T, Yamada K, Ishida T, Yoshida M, Azuma T, Mizuno M. Lactococcus lactis subsp. cremoris FC alleviates symptoms of colitis induced by dextran sulfate sodium in mice. Int Immunopharmacol 2009; 9: 1444-1451. https://doi.org/10.1016/j.intimp.2009.08.018
  19. Murthy S, Flanigan A, Coppola D, Buelow R. RDP58, a locally active TNF inhibitor, is effective in the dextran sulphate mouse model of chronic colitis. Inflamm Res 2002; 51: 522-531. https://doi.org/10.1007/PL00012423
  20. Rogler G, Andus T. Cytokines in inflammatory bowel disease. World J Surg 1998; 22: 382-389. https://doi.org/10.1007/s002689900401
  21. Owczarek D, Cibor D, Szczepanek M, Mach T. Biological therapy of inflammatory bowel disease. Pol Arch Med Wewn 2009; 119: 84-88.
  22. 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
  23. 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
  24. 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
  25. Summers RW. Novel and future medical management of inflammatory bowel disease. Surg Clin North Am 2007; 87: 727-741. https://doi.org/10.1016/j.suc.2007.03.004
  26. Ruyssers NE, De Winter BY, De Man JG, Loukas A, Pearson MS, Weinstock JV, Van den Bossche RM, Martinet W, Pelckmans PA, Moreels TG. Therapeutic potential of helminth soluble proteins in TNBS-induced colitis in mice. Inflamm Bowel Dis 2009; 15: 491-500. https://doi.org/10.1002/ibd.20787
  27. 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. https://doi.org/10.4049/jimmunol.181.11.7751
  28. Dunne DW, Cooke A. A worm's eye view of the immune system: Consequences for evolution of human autoimmune disease. Nat Rev Immunol 2005; 5: 420-426. https://doi.org/10.1038/nri1601
  29. Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G, Wahl SM. Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 2003; 198: 1875-1886. https://doi.org/10.1084/jem.20030152
  30. Huber S, Schramm C, Lehr HA, Mann A, Schmitt S, Becker C, Protschka M, Galle PR, Neurath MF, Blessing M. Cutting edge: TGF-beta signaling is required for the in vivo expansion and immunosuppressive capacity of regulatory CD4+CD25+ T cells. J Immunol 2004; 173: 6526-6531. https://doi.org/10.4049/jimmunol.173.11.6526

피인용 문헌

  1. Trichinella spiralisimmunomodulation: an interactive multifactorial process vol.9, pp.7, 2012, https://doi.org/10.1586/1744666x.2013.811187
  2. Helminth Regulation of Immunity : A Three-pronged Approach to Treat Colitis vol.22, pp.10, 2016, https://doi.org/10.1097/mib.0000000000000889
  3. Regulatory T Cell and Forkhead Box Protein 3 as Modulators of Immune Homeostasis vol.8, pp.None, 2012, https://doi.org/10.3389/fimmu.2017.00605
  4. Biodegradable Chitosan Decreases the Immune Response to Trichinella spiralis in Mice vol.22, pp.11, 2012, https://doi.org/10.3390/molecules22112008
  5. Adoptive transfer of Trichinella spiralis-activated macrophages can ameliorate both Th1- and Th2-activated inflammation in murine models vol.9, pp.None, 2012, https://doi.org/10.1038/s41598-019-43057-1
  6. Trichinella spiralis: inflammation modulator vol.94, pp.None, 2012, https://doi.org/10.1017/s0022149x20000802
  7. Infection with Toxocara canis Inhibits the Production of IgE Antibodies to α-Gal in Humans: Towards a Conceptual Framework of the Hygiene Hypothesis? vol.8, pp.2, 2012, https://doi.org/10.3390/vaccines8020167
  8. Potential of human helminth therapy for resolution of inflammatory bowel disease: The future ahead vol.232, pp.None, 2012, https://doi.org/10.1016/j.exppara.2021.108189