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Shigella flexneri Inhibits Intestinal Inflammation by Modulation of Host Sphingosine-1-Phosphate in Mice

  • Kim, Young-In (Laboratory of Microbiology, College of Pharmacy, Ajou University) ;
  • Yang, Jin-Young (Mucosal Immunology Laboratory, Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Ko, Hyun-Jeong (Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University) ;
  • Kweon, Mi-Na (Mucosal Immunology Laboratory, Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Chang, Sun-Young (Laboratory of Microbiology, College of Pharmacy, Ajou University)
  • Received : 2013.12.28
  • Accepted : 2014.04.01
  • Published : 2014.04.30
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Abstract

Infection with invasive Shigella species results in intestinal inflammation in humans but no symptoms in adult mice. To investigate why adult mice are resistant to invasive shigellae, 6~8-week-old mice were infected orally with S. flexneri 5a. Shigellae successfully colonized the small and large intestines. Mild cell death was seen but no inflammation. The infected bacteria were cleared 24 hours later. Microarray analysis of infected intestinal tissue showed that several genes that are involved with the sphingosine-1-phosphate (S1P) signaling pathway, a lipid mediator which mediates immune responses, were altered significantly. Shigella infection of a human intestinal cell line modulated host S1P-related genes to reduce S1P levels. In addition, co-administration of S1P with shigellae could induce inflammatory responses in the gut. Here we propose that Shigella species have evasion mechanisms that dampen host inflammatory responses by lowering host S1P levels in the gut of adult mice.

Keywords

References

  1. Kotloff, K. L., J. P. Winickoff, B. Ivanoff, J. D. Clemens, D. L. Swerdlow, P. J. Sansonetti, G. K. Adak, and M. M. Levine. 1999. Global burden of Shigella infections: implications for vaccine development and implementation of control strategies. Bull. World Health Organ. 77: 651-666.
  2. Ogawa, M., Y. Handa, H. Ashida, M. Suzuki, and C. Sasakawa. 2008. The versatility of Shigella effectors. Nat. Rev. Microbiol. 6: 11-16. https://doi.org/10.1038/nrmicro1814
  3. Kweon, M. N. 2008. Shigellosis: the current status of vaccine development. Curr. Opin. Infect. Dis. 21: 313-318. https://doi.org/10.1097/QCO.0b013e3282f88b92
  4. Ashida, H., M. Ogawa, H. Mimuro, T. Kobayashi, T. Sanada, and C. Sasakawa. 2011. Shigella are versatile mucosal pathogens that circumvent the host innate immune system. Curr. Opin. Immunol. 23: 448-455. https://doi.org/10.1016/j.coi.2011.06.001
  5. Shim, D. H., T. Suzuki, S. Y. Chang, S. M. Park, P. J. Sansonetti, C. Sasakawa, and M. N. Kweon. 2007. New animal model of shigellosis in the Guinea pig: its usefulness for protective efficacy studies. J. Immunol. 178: 2476-2482. https://doi.org/10.4049/jimmunol.178.4.2476
  6. Fernandez, M. I., A. Thuizat, T. Pedron, M. Neutra, A. Phalipon, and P. J. Sansonetti. 2003. A newborn mouse model for the study of intestinal pathogenesis of shigellosis. Cell. Microbiol. 5: 481-491. https://doi.org/10.1046/j.1462-5822.2003.00295.x
  7. Shim, D. H., S. Ryu, and M. N. Kweon. 2010. Defensins play a crucial role in protecting mice against oral Shigella flexneri infection. Biochem. Biophys. Res. Commun. 401: 554-560. https://doi.org/10.1016/j.bbrc.2010.09.100
  8. Ashida, H., H. Mimuro, M. Ogawa, T. Kobayashi, T. Sanada, M. Kim, and C. Sasakawa. 2011. Cell death and infection: a double-edged sword for host and pathogen survival. J. Cell Biol. 195: 931-942. https://doi.org/10.1083/jcb.201108081
  9. Bergsbaken, T., S. L. Fink, and B. T. Cookson. 2009. Pyroptosis: host cell death and inflammation. Nat. Rev. Microbiol. 7: 99-109. https://doi.org/10.1038/nrmicro2070
  10. Sanada, T., M. Kim, H. Mimuro, M. Suzuki, M. Ogawa, A. Oyama, H. Ashida, T. Kobayashi, T. Koyama, S. Nagai, Y. Shibata, J. Gohda, J. Inoue, T. Mizushima, and C. Sasakawa. 2012. The Shigella flexneri effector OspI deamidates UBC13 to dampen the inflammatory response. Nature 483: 623-626. https://doi.org/10.1038/nature10894
  11. Ogawa, M., T. Yoshimori, T. Suzuki, H. Sagara, N. Mizushima, and C. Sasakawa. 2005. Escape of intracellular Shigella from autophagy. Science 307: 727-731. https://doi.org/10.1126/science.1106036
  12. Ogawa, M., Y. Yoshikawa, T. Kobayashi, H. Mimuro, M. Fukumatsu, K. Kiga, Z. Piao, H. Ashida, M. Yoshida, S. Kakuta, T. Koyama, Y. Goto, T. Nagatake, S. Nagai, H. Kiyono, M. Kawalec, J. M. Reichhart, and C. Sasakawa. 2011. A Tecpr1-dependent selective autophagy pathway targets bacterial pathogens. Cell Host. Microbe. 9: 376-389.
  13. Chang, S. Y., S. N. Lee, J. Y. Yang, D. W. Kim, J. H. Yoon, H. J. Ko, M. Ogawa, C. Sasakawa, and M. N. Kweon. 2013. Autophagy controls an intrinsic host defense to bacteria by promoting epithelial cell survival: a murine model. PLoS One 8: e81095. https://doi.org/10.1371/journal.pone.0081095
  14. Yang, J. Y., S. N. Lee, S. Y. Chang, H. J. Ko, S. Ryu, and M. N. Kweon. 2014. A mouse model of shigellosis by intraperitoneal infection. J. Infect. Dis. 209: 203-215. https://doi.org/10.1093/infdis/jit399
  15. Le Stunff, H., A. Mikami, P. Giussani, J. P. Hobson, P. S. Jolly, S. Milstien, and S. Spiegel. 2004. Role of sphingosine- 1-phosphate phosphatase 1 in epidermal growth factor- induced chemotaxis. J. Biol. Chem. 279: 34290-34297. https://doi.org/10.1074/jbc.M404907200
  16. Ashida, H., M. Ogawa, M. Kim, H. Mimuro, and C. Sasakawa. 2011. Bacteria and host interactions in the gut epithelial barrier. Nat. Chem. Biol. 8: 36-45. https://doi.org/10.1038/nchembio.741
  17. Sansonetti, P. J. 2006. Shigellosis: an old disease in new clothes? PLoS Med. 3: e354. https://doi.org/10.1371/journal.pmed.0030354
  18. Le Stunff, H., S. Milstien, and S. Spiegel. 2004. Generation and metabolism of bioactive sphingosine-1-phosphate. J. Cell. Biochem. 92: 882-899. https://doi.org/10.1002/jcb.20097
  19. Spiegel, S. and S. Milstien. 2011. The outs and the ins of sphingosine-1-phosphate in immunity. Nat. Rev. Immunol. 11: 403-415. https://doi.org/10.1038/nri2974
  20. Chi, H. 2011. Sphingosine-1-phosphate and immune regulation: trafficking and beyond. Trends Pharmacol. Sci. 32: 16-24. https://doi.org/10.1016/j.tips.2010.11.002
  21. Alvarez, S. E., K. B. Harikumar, N. C. Hait, J. Allegood, G. M. Strub, E. Y. Kim, M. Maceyka, H. Jiang, C. Luo, T. Kordula, S. Milstien, and S. Spiegel. 2010. Sphingosine-1- phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2. Nature 465: 1084-1088. https://doi.org/10.1038/nature09128
  22. Teijaro, J. R., K. B. Walsh, S. Cahalan, D. M. Fremgen, E. Roberts, F. Scott, E. Martinborough, R. Peach, M. B. Oldstone, and H. Rosen. 2011. Endothelial cells are central orchestrators of cytokine amplification during influenza virus infection. Cell 146: 980-991. https://doi.org/10.1016/j.cell.2011.08.015
  23. Ashida, H., M. Ogawa, H. Mimuro, and C. Sasakawa. 2009. Shigella infection of intestinal epithelium and circumvention of the host innate defense system. Curr. Top. Microbiol. Immunol. 337: 231-255.
  24. Tran Van Nhieu, G., R. Bourdet-Sicard, G. Dumenil, A. Blocker, and P. J. Sansonetti. 2000. Bacterial signals and cell responses during Shigella entry into epithelial cells. Cell. Microbiol. 2: 187-193. https://doi.org/10.1046/j.1462-5822.2000.00046.x

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