IL-33 receptor (T1/ST2) signalling is necessary to prevent the development of encephalitis in mice infected with Toxoplasma gondii.
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.
Jones
Leigh A
LA
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
Roberts
Fiona
F
Nickdel
Mohammad B
MB
Brombacher
Frank
F
McKenzie
Andrew N J
AN
Henriquez
Fiona L
FL
Alexander
James
J
Roberts
Craig W
CW
D000818:Animals; D001835:Body Weight; D001921:Brain / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D004660:Encephalitis / Q000276:immunology* / Q000469:parasitology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D000072179:Interleukin-1 Receptor-Like 1 Protein; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D014122:Toxoplasma / Q000254:growth & development / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000276:immunology* / Q000469:parasitology; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D053662:Interleukin-4 Receptor alpha Subunit
D007371:Interferon-gamma; D000072179:Interleukin-1 Receptor-Like 1 Protein; D015847:Interleukin-4; D052247:Nitric Oxide Synthase Type II; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin; D014409:Tumor Necrosis Factor-alpha; C486189:Il1rl1 protein, mouse; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit