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T1/ST2 is an immunoregulatory protein of the IL-1 receptor family that has recently been reported as being a component of the IL-33 receptor. IL-33 is a newly described cytokine known to amplify the Th2 response and reduce production of Th1 cytokines. The function of T1/ST2 during Toxoplasma gondii infection is as yet undescribed. Given the requirement of a balanced type 1/type 2 response for effective control of parasite number and immunopathology, it is likely that T1/ST2 may play a part in aiding this process. Accordingly, we have shown that T1/ST2 mRNA transcripts are upregulated in the brains of mice infected with T. gondii and that mice deficient in T1/ST2 demonstrated increased susceptibility to infection with T. gondii that correlated with increased pathology and greater parasite burden in the brains. Real-time PCR analysis of cerebral cytokine levels revealed increased mRNA levels of iNOS, IFN-gamma and TNF-alpha in infected T1/ST2(-/-) mice. These effects were independent of changes in IL-10 production. This study provides the first evidence of a specific role for IL-33 receptor signalling in the brain as well as highlighting the requirement of this mechanism in limiting infection with an intracellular parasite.

Original publication

DOI

10.1002/eji.200939705

Type

Journal

European journal of immunology

Publication Date

02/2010

Volume

40

Pages

426 - 436

Addresses

Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.

Keywords

Brain, Animals, Mice, Inbred BALB C, Mice, Knockout, Mice, Toxoplasma, Encephalitis, Toxoplasmosis, Animal, Body Weight, Tumor Necrosis Factor-alpha, Receptors, Cell Surface, Receptors, Interleukin, Interleukin-4, Enzyme-Linked Immunosorbent Assay, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Female, Male, Nitric Oxide Synthase Type II, Interferon-gamma, Transcriptional Activation, Interleukin-1 Receptor-Like 1 Protein