The sphingosine-1-phosphate analogue FTY720 impairs mucosal immunity and clearance of the enteric pathogen Citrobacter rodentium

Infection and Immunity

Volumn 80, Issue 8, 2012, Pages 2712-2723

  Murphy, Carola T ^a   Hall, Lindsay J ^a,b   Hurley, Grainne ^a   Quinlan, Aoife ^a   MacSharry, John ^a   Shanahan, Fergus ^a   Nally, Kenneth ^a   Melgar, Silvia ^a  

^a UNIVERSITY COLLEGE CORK   (Ireland)

^b INSTITUTE OF FOOD RESEARCH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

FINGOLIMOD;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; B LYMPHOCYTE; CITROBACTER RODENTIUM; COLITIS; CONTROLLED STUDY; DENDRITIC CELL; ESCHERICHIA COLI; FEMALE; GOAT; HAMSTER; HISTOPATHOLOGY; HOST SUSCEPTIBILITY; IMMUNE RESPONSE; LYMPHOCYTOPENIA; MOUSE; MUCOSAL IMMUNITY; NEUTROPHIL; NONHUMAN; PRIORITY JOURNAL; RAT; T LYMPHOCYTE; TH1 CELL;

ANIMALS; CITROBACTER RODENTIUM; ENTEROBACTERIACEAE INFECTIONS; FEMALE; GENE EXPRESSION REGULATION; IMMUNITY, MUCOSAL; IMMUNOSUPPRESSIVE AGENTS; LYMPHOPENIA; MICE; MICE, INBRED STRAINS; PROPYLENE GLYCOLS; RNA, MESSENGER; SPECIFIC PATHOGEN-FREE ORGANISMS; SPHINGOSINE;

EID: 84864802528     PISSN: 00199567     EISSN: 10985522     Source Type: Journal    
DOI: 10.1128/IAI.06319-11     Document Type: Article

References (58)

1. Brinkmann V, et al. 2010. Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat. Rev. Drug Discov. 9:883-897.
2. Brinkmann V, et al. 2002. The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J. Biol. Chem. 277:21453-21457.
3. Brinkmann V, Lynch KR. 2002. FTY720: targeting G-protein-coupled receptors for sphingosine 1-phosphate in transplantation and autoimmunity. Curr. Opin. Immunol. 14:569-575.
4. Budde K, et al. 2002. First human trial of FTY720, a novel immunomodulator, in stable renal transplant patients. J. Am. Soc. Nephrol. 13:1073-1083.
5. Chi H, Flavell RA. 2005. Cutting edge: regulation of T cell trafficking and primary immune responses by sphingosine 1-phosphate receptor 1. J. Immunol. 174:2485-2488.
6. Chiba K, Matsuyuki H, Maeda Y, Sugahara K. 2006. Role of sphingosine 1-phosphate receptor type 1 in lymphocyte egress from secondary lymphoid tissues and thymus. Cell. Mol. Immunol. 3:11-19.
7. Cohen JA, et al. 2010. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N. Engl. J. Med. 362:402-415.
8. Collins W, et al. 2010. Long-term safety of oral fingolimod (FTY720) in relapsing multiple sclerosis: integrated analyses of phase 2 and 3 studies. Mult. Scler. 16:S295.
9. Contag CH, et al. 1995. Photonic detection of bacterial pathogens in living hosts. Mol. Microbiol. 18:593-603.
10. Costa GL, et al. 2001. Adoptive immunotherapy of experimental autoimmune encephalomyelitis via T cell delivery of the IL-12 p40 subunit. J. Immunol. 167:2379-2387.
11. Daniel C, et al. 2007. FTY720 ameliorates Th1-mediated colitis in mice by directly affecting the functional activity of CD4_ CD25_ regulatory T cells. J. Immunol. 178:2458-2468.
12. Daniel C, et al. 2007. FTY720 ameliorates oxazolone colitis in mice by directly affecting T helper type 2 functions. Mol. Immunol. 44:3305-3316.
13. Dann SM, et al. 2008. IL-6-dependent mucosal protection prevents establishment of a microbial niche for attaching/effacing lesion-forming enteric bacterial pathogens. J. Immunol. 180:6816-6826.
14. Deguchi Y, et al. 2006. The S1P receptor modulator FTY720 prevents the development of experimental colitis in mice. Oncol. Rep. 16:699-703.
15. Edinger M, Hoffmann P, Contag CH, Negrin RS. 2003. Evaluation of effector cell fate and function by in vivo bioluminescence imaging. Methods 31:172-179.
16. Eigenbrod S, Derwand R, Jakl V, Endres S, Eigler A. 2006. Sphingosine kinase and sphingosine-1-phosphate regulate migration, endocytosis and apoptosis of dendritic cells. Immunol. Invest. 35:149-165.
17. Francis KP, et al. 2001. Visualizing pneumococcal infections in the lungs of live mice using bioluminescent Streptococcus pneumoniae transformed with a novel gram-positive lux transposon. Infect. Immun. 69:3350-3358.
18. Fujii R, et al. 2006. FTY720 suppresses CD4_ CD44high CD62L_ effector memory T cell-mediated colitis. Am. J. Physiol. Gastrointest. Liver Physiol. 291:G267-G274.
19. Garber K. 2008. Infections cast cloud over Novartis' MS therapy. Nat. Biotechnol. 26:844-845.
20. Gobert AP, et al. 2004. Protective role of arginase in a mouse model of colitis. J. Immunol. 173:2109-2117.
21. Gräler MH, Goetzl EJ. 2004. The immunosuppressant FTY720 downregulates sphingosine 1-phosphate G-protein-coupled receptors. FASEB J. 18:551-553.
22. Higgins LM, Frankel G, Douce G, Dougan G, MacDonald TT. 1999. Citrobacter rodentium infection in mice elicits a mucosal Th1 cytokine response and lesions similar to those in murine inflammatory bowel disease. Infect. Immun. 67:3031-3039.
23. Horga A, Castillo J, Montalban X. 2010. Fingolimod for relapsing multiple sclerosis: an update. Expert Opin. Pharmacother. 11:1183-1196.
24. Hoshino Y, et al. 1996. FTY720, a novel immunosuppressant possessing unique mechanisms. II. Long-term graft survival induction in rat heterotopic cardiac allografts and synergistic effect in combination with cyclosporine A. Transplant. Proc. 28:1060-1061.
25. Ishigame H, et al. 2009. Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity 30:108-119.
26. Ito R, et al. 2008. Involvement of IL-17A in the pathogenesis of DSSinduced colitis in mice. Biochem. Biophys. Res. Commun. 377:12-16.
27. Kappos L, et al. 2006. Oral fingolimod (FTY720) for relapsing multiple sclerosis. N. Engl. J. Med. 355:1124-1140.
28. Kappos L, et al. 2010. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N. Engl. J. Med. 362:387-401.
29. Kenny B, et al. 1997. Enteropathogenic E. coli (EPEC) transfers its receptor for intimate adherence into mammalian cells. Cell 91:511-520.
30. Kersh EN, et al. 2009. Evaluation of the lymphocyte trafficking drug FTY720 in SHIVSF162P3-infected rhesus macaques. J. Antimicrob. Chemother. 63:758-762.
31. Lan YY, et al. 2005. The sphingosine-1-phosphate receptor agonist FTY720 modulates dendritic cell trafficking in vivo. Am. J. Transplant. 5:2649-2659.
32. Lebeis SL, Bommarius B, Parkos CA, Sherman MA, Kalman D. 2007. TLR signaling mediated by MyD88 is required for a protective innate immune response by neutrophils to Citrobacter rodentium. J. Immunol. 179:566-577.
33. Livak KJ, Schmittgen TD. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(_Delta Delta C(T)) Method. Methods 25:402-408.
34. Maaser C, et al. 2004. Clearance of Citrobacter rodentium requires B cells but not secretory immunoglobulin A (IgA) or IgM antibodies. Infect. Immun. 72:3315-3324.
35. Mehling M, Johnson TA, Antel J, Kappos L, Bar-Or A. 2011. Clinical immunology of the sphingosine 1-phosphate receptor modulator fingolimod (FTY720) in multiple sclerosis. Neurology 76(Suppl 3):S20-S27.
36. Mizushima T, et al. 2004. Therapeutic effects of a new lymphocyte homing reagent FTY720 in interleukin-10 gene-deficient mice with colitis. Inflamm. Bowel Dis. 10:182-192.
37. Mundy R, MacDonald TT, Dougan G, Frankel G, Wiles S. 2005. Citrobacter rodentium of mice and man. Cell. Microbiol. 7:1697-1706.
38. Murphy CT, et al. 2010. Use of bioluminescence imaging to track neutrophil migration and its inhibition in experimental colitis. Clin. Exp. Immunol. 162:188-196.
39. Murphy CT, et al. 2010. Technical advance: function and efficacy of an {alpha}4-integrin antagonist using bioluminescence imaging to detect leukocyte trafficking in murine experimental colitis. J. Leukoc. Biol. 88: 1271-1278.
40. Rocchetta HL, et al. 2001. Validation of a noninvasive, real-time imaging technology using bioluminescent Escherichia coli in the neutropenic mouse thigh model of infection. Antimicrob. Agents Chemother. 45:129-137.
41. Sartor RB. 1994. Cytokines in intestinal inflammation: pathophysiological and clinical considerations. Gastroenterology 106:533-539.
42. Schmouder R, Boulton C, Wang N, David OJ. 2010. Effects of fingolimod on antibody response following steady-state dosing in healthy volunteers: a 4-week randomised, placebo-controlled study (P412). Mult. Scler 16(Suppl 10):S135.
43. Sheikh AY, et al. 2007. Molecular imaging of bone marrow mononuclear cell homing and engraftment in ischemic myocardium. Stem Cells 25: 2677-2684.
44. Shiomi H, et al. 2010. Gamma interferon produced by antigen-specific CD4_ T cells regulates the mucosal immune responses to Citrobacter rodentium infection. Infect. Immun. 78:2653-2666.
45. Simmons CP, et al. 2003. Central role for B lymphocytes and CD4_ T cells in immunity to infection by the attaching and effacing pathogen Citrobacter rodentium. Infect. Immun. 71:5077-5086.
46. Simmons CP, et al. 2002. Impaired resistance and enhanced pathology during infection with a noninvasive, attaching-effacing enteric bacterial pathogen, Citrobacter rodentium, in mice lacking IL-12 or IFN-gamma. J. Immunol. 168:1804-1812.
47. Sinha RK, Park C, Hwang IY, Davis MD, Kehrl JH. 2009. B lymphocytes exit lymph nodes through cortical lymphatic sinusoids by a mechanism independent of sphingosine-1-phosphate-mediated chemotaxis. Immunity 30:434-446.
48. Smith AD, Botero S, Shea-Donohue T, Urban JF, Jr. 2011. The pathogenicity of an enteric Citrobacter rodentium infection is enhanced by deficiencies in the antioxidants selenium and vitamin E. Infect. Immun. 79: 1471-1478.
49. Southey A, et al. 1997. Pathophysiological role of nitric oxide in rat experimental colitis. Int. J. Immunopharmacol. 19:669-676.
50. Spehlmann ME, et al. 2009. CXCR2-dependent mucosal neutrophil influx protects against colitis-associated diarrhea caused by an attaching/ effacing lesion-forming bacterial pathogen. J. Immunol. 183:3332-3343.
51. Sweeney TJ, et al. 1999. Visualizing the kinetics of tumor-cell clearance in living animals. Proc. Natl. Acad. Sci. U. S. A. 96:12044-12049.
52. Thangada S, et al. 2010. Cell-surface residence of sphingosine 1-phosphate receptor 1 on lymphocytes determines lymphocyte egress kinetics. J. Exp. Med. 207:1475-1483.
53. Vallance BA, et al. 2002. Modulation of inducible nitric oxide synthase expression by the attaching and effacing bacterial pathogen Citrobacter rodentium in infected mice. Infect. Immun. 70:6424-6435.
54. Vallance BA, Deng W, Knodler LA, Finlay BB. 2002. Mice lacking T and B lymphocytes develop transient colitis and crypt hyperplasia yet suffer impaired bacterial clearance during Citrobacter rodentium infection. Infect. Immun. 70:2070-2081.
55. Wiles S, et al. 2004. Organ specificity, colonization and clearance dynamics in vivo following oral challenges with the murine pathogen Citrobacter rodentium. Cell. Microbiol. 6:963-972.
56. Wolf AM, et al. 2009. The sphingosine 1-phosphate receptor agonist FTY720 potently inhibits regulatory T cell proliferation in vitro and in vivo. J. Immunol. 183:3751-3760.
57. Zheng Y, et al. 2008. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat. Med. 14:282-289.
58. Zhi L, et al. 2011. FTY720 blocks egress of T cells in part by abrogation of their adhesion on the lymph node sinus. J. Immunol. 187:2244-2251.