The Unexpected Role for the Aryl Hydrocarbon Receptor on Susceptibility to Experimental Toxoplasmosis

• Published in: BioMed research international 2010-01, Vol.2010 (2010), p.1-15
• Main Authors: Sanchez, Yuriko, de Dios Rosado, Juan, Vega, Libia, Elizondo, Guillermo, Estrada-Muñiz, Elizabeth, Saavedra, Rafael, Juárez, Imelda, Rodríguez-Sosa, Miriam
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Protozoan - immunology; Ascitic Fluid - metabolism; Biomedical research; Brain - immunology; Cysts; Cytokines; Female; Flow Cytometry; GATA3 Transcription Factor - genetics; GATA3 Transcription Factor - metabolism; Immune system; Immunity, Innate - immunology; Inbreeding; Interferon-gamma - biosynthesis; Interferon-gamma - blood; Interferon-gamma - genetics; Interleukins - biosynthesis; Interleukins - blood; Lipoxins - biosynthesis; Lipoxins - genetics; Liver - immunology; Liver - pathology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mortality; Nitric oxide; Parasites; Proteins; Receptors, Aryl Hydrocarbon - deficiency; Receptors, Aryl Hydrocarbon - genetics; Receptors, Aryl Hydrocarbon - immunology; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Spleen - immunology; Toxoplasma - immunology; Toxoplasma gondii; Toxoplasmosis, Animal - immunology; Toxoplasmosis, Animal - metabolism; Toxoplasmosis, Animal - pathology; Tumor Necrosis Factor-alpha - blood
• ISSN: 1110-7243; 2314-6133; 1110-7251; 2314-6141
• DOI: 10.1155/2010/505694

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)-α, 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-γ mRNA. Additionally, peritoneal exudate cells from AhR-/- mice produced higher levels of IL-12 and IFN-γ but lower TLR2 expression than WT mice. These findings suggest a role for AhR in limiting the inflammatory response during toxoplasmosis.