TY  - JOUR
  - Carola T. Murphy, Lindsay J. Hall, Grainne Hurley, Aoife Quinlan, John MacSharry, Fergus Shanahan, Kenneth Nally, Silvia Melgar
  - 2012
  - August
  - Infection and Immunity
  - The Spingosine-1-Phosphate Analogue FTY720 Impairs Mucosal Immunity and Clearance of the Enteric Pathogen Citrobacter rodentium
  - Published
  - ()
  - S1P, infection, immunity, multiple sclerosis
  - 80
  - 8
  - 2712
  - 2723
  - The sphingosine-1-phosphate (S1P) analogue, FTY720, is therapeutically efficaciousin multiple sclerosis and in the prevention of transplant rejection. It preventsmigration of lymphocytes to sites of pathology by trapping them within the peripherallymph nodes, the mesenteric lymph nodes (MLNs) and Peyer's patches. However,evidence suggests that its clinical use may increase the risk of mucosal infections. Weinvestigated the impact of FTY720 treatment on susceptibility to gastrointestinalinfection with the mouse enteric pathogen, Citrobacter rodentium (C. rodentium).This attaching and effacing bacterium induces a transient bacterial colitis inimmunocompetent mice, which resembles human infection with pathogenicEscherichia coli. FTY720 treatment induced peripheral blood lymphopenia, trappedlymphocytes in the MLNs and prevented clearance of bacteria when mice wereinfected with luciferase-tagged C. rodentium. FTY720-treated C. rodentium-infectedmice had enhanced colonic inflammation, with significantly higher colon mass, colonhistopathology and neutrophil infiltration, when compared with vehicle-infectedanimals. In addition, FTY720-treated infected mice had significantly lower numbersof colonic dendritic cells, macrophages and T cells. Gene expression analysisdemonstrated that FTY720-treated infected mice had an impaired innate immuneresponse and a blunted mucosal adaptive immune response including Th1 cytokines. .The data demonstrate that the S1P analogue, FTY720, adversely affects the immuneresponse and clearance of C. rodentium.
  - American Society for Microbiology
  - Science Foundation Ireland
  - The Alimentary Pharmabiotic Centre is funded by Science Foundation Ireland (SFI) and we and our work are supported by SFI grants 02/CE/B124 and 07/CE/B1368.
DA  - 2012/08
ER  - 

@article{V156205521,
   = {Carola T. Murphy,  Lindsay J. Hall and  Grainne Hurley,  Aoife Quinlan and  John MacSharry,  Fergus Shanahan and  Kenneth Nally,  Silvia Melgar },
   = {2012},
   = {August},
   = {Infection and Immunity},
   = {The Spingosine-1-Phosphate Analogue FTY720 Impairs Mucosal Immunity and Clearance of the Enteric Pathogen Citrobacter rodentium},
   = {Published},
   = {()},
   = {S1P, infection, immunity, multiple sclerosis},
   = {80},
   = {8},
  pages = {2712--2723},
   = {{The sphingosine-1-phosphate (S1P) analogue, FTY720, is therapeutically efficaciousin multiple sclerosis and in the prevention of transplant rejection. It preventsmigration of lymphocytes to sites of pathology by trapping them within the peripherallymph nodes, the mesenteric lymph nodes (MLNs) and Peyer's patches. However,evidence suggests that its clinical use may increase the risk of mucosal infections. Weinvestigated the impact of FTY720 treatment on susceptibility to gastrointestinalinfection with the mouse enteric pathogen, Citrobacter rodentium (C. rodentium).This attaching and effacing bacterium induces a transient bacterial colitis inimmunocompetent mice, which resembles human infection with pathogenicEscherichia coli. FTY720 treatment induced peripheral blood lymphopenia, trappedlymphocytes in the MLNs and prevented clearance of bacteria when mice wereinfected with luciferase-tagged C. rodentium. FTY720-treated C. rodentium-infectedmice had enhanced colonic inflammation, with significantly higher colon mass, colonhistopathology and neutrophil infiltration, when compared with vehicle-infectedanimals. In addition, FTY720-treated infected mice had significantly lower numbersof colonic dendritic cells, macrophages and T cells. Gene expression analysisdemonstrated that FTY720-treated infected mice had an impaired innate immuneresponse and a blunted mucosal adaptive immune response including Th1 cytokines. .The data demonstrate that the S1P analogue, FTY720, adversely affects the immuneresponse and clearance of C. rodentium.}},
   = {American Society for Microbiology},
   = {Science Foundation Ireland},
   = {The Alimentary Pharmabiotic Centre is funded by Science Foundation Ireland (SFI) and we and our work are supported by SFI grants 02/CE/B124 and 07/CE/B1368.},
  source = {IRIS}
}