The unexpected role for the aryl hydrocarbon receptor on susceptibility to experimental toxoplasmosis.
The aryl hydrocarbon receptor (AhR) is part of a signaling system that is mainly triggered by xenobiotic agents. Increasing evidence suggests that AhR may regulate immunity to infections. To determine the role of AhR in the outcome of toxoplasmosis, we used AhR-/- and wild-type (WT) mice. Following an intraperitoneal infection with Toxoplasma gondii (T. gondii), AhR-/- mice succumbed significantly faster than WT mice and displayed greater liver damage as well as higher serum levels of tumor necrosis factor (TNF)-alpha, nitric oxide (NO), and IgE but lower IL-10 secretion. Interestingly, lower numbers of cysts were found in their brains. Increased mortality was associated with reduced expression of GATA-3, IL-10, and 5-LOX mRNA in spleen cells but higher expression of IFN-gamma mRNA. Additionally, peritoneal exudate cells from AhR-/- mice produced higher levels of IL-12 and IFN-gamma but lower TLR2 expression than WT mice. These findings suggest a role for AhR in limiting the inflammatory response during toxoplasmosis.
Sanchez
Yuriko
Y
Unidad de Biomedicina, Facultad de Estudios Superiores-Iztacala, Universidad Nacional Autónoma de México (UNAM), CP 54090, o. Tlalnepantla, Edo. de México, Mexico.
Rosado
Juan de Dios
Jde D
Vega
Libia
L
Elizondo
Guillermo
G
Estrada-Muñiz
Elizabeth
E
Saavedra
Rafael
R
Juárez
Imelda
I
Rodríguez-Sosa
Miriam
M
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D001202:Ascitic Fluid / Q000378:metabolism; D001921:Brain / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D007113:Immunity, Innate / Q000276:immunology; D007178:Inbreeding; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D007378:Interleukins / Q000096:biosynthesis / Q000097:blood; D044045:Lipoxins / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000953:Antigens, Protozoan; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D007378:Interleukins; D044045:Lipoxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D014409:Tumor Necrosis Factor-alpha; C040527:lipoxin A4; C094052:soluble tachyzoite antigen, Toxoplasma gondii; D007371:Interferon-gamma