Interleukin 17 receptor signaling is deleterious during Toxoplasma gondii infection in susceptible BL6 mice.
Th17 cells are involved in host defense against several pathogens. Using interleukin (IL) 17RA-deficient mice, we demonstrated reduced ileitis with diminished neutrophil recruitment and inflammatory lesions in the ileum, in the regional lymph node, in the spleen, and in the liver at day 7 and prolonged survival after Toxoplasma gondii infection. In addition, IL-17A antibody neutralization reduced inflammation and enhanced survival in BL6 mice. Diminished inflammation is associated with augmented interferon (IFN) gamma serum levels and enhanced production of IL-10 and IFN-gamma in cultured splenocytes upon antigen restimulation. Finally, cyst load and inflammation in the brain at 40 days are greater in surviving BL6 mice than in IL-17RA-deficient mice. In conclusion, oral T. gondii infection increases IL-17 expression and contributes to the inflammatory response, and IL-17 neutralization has a partial protective effect against fatal T. gondii-associated inflammation.
Guiton
Rachel
R
Unité Mixte de Recherche (UMR), 0483 Université, Institut National de la Recherche Agronomique (INRA), Immunologie Parasitaire et Vaccinologie, Biothérapies Anti-Infectieuses, Université François Rabelais, Unité de Formation et de Recherche des Sciences Pharmaceutiques, Tours, France. rachelguiton@gmail.com
Vasseur
Virginie
V
Charron
Sabine
S
Arias
Marbel Torres
MT
Van Langendonck
Nathalie
N
Buzoni-Gatel
Dominique
D
Ryffel
Bernhard
B
Dimier-Poisson
Isabelle
I
D000818:Animals; D001921:Brain / Q000469:parasitology / Q000473:pathology; D007082:Ileum / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053722:Receptors, Interleukin-17 / Q000172:deficiency / Q000378:metabolism*; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000473:pathology
C491673:Il17ra protein, mouse; D053722:Receptors, Interleukin-17; D016753:Interleukin-10; D007371:Interferon-gamma