期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 40, 期 2, 页码 426-436出版社
WILEY
DOI: 10.1002/eji.200939705
关键词
Encephalitis; IL-33; IL-33 receptor; Th1/Th2; Toxoplasma
类别
资金
- Carnegie Trust for the Universities of Scotland
- Wellcome Trust
- Royal Society
- National Research Foundation, South Africa
- MRC [MC_U105178805] Funding Source: UKRI
- Medical Research Council [MC_U105178805] Funding Source: researchfish
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.
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