STAT6 signalling is important in CD8 T-cell activation and defence against Toxoplasma gondii infection in the brain.
Signal transducer and activator of transcription (STAT) 6 is a molecule involved in interleukin (IL)-4 and -13 signalling. We investigated the role of STAT6 signalling in Toxoplasma gondii-infected mice using STAT6-deficient (STAT6(-/-)) and wild-type (WT) mice. A significantly larger number of cysts were recovered from the brain in STAT6(-/-) than in WT mice on days 28 and 56 post-infection. CD8(+) T cells in cerebrospinal fluid and spleen stimulated with T. gondii antigen produced higher levels of interferon (IFN)-gamma in WT than in STAT6(-/-) mice. CD8(+) T-cell function, estimated by expression of CD25 and cytotoxic activity, was lower in STAT6(-/-) than in WT mice. Transfer of CD8(+) but not CD4(+) T cells, purified from infected WT mice, into STAT6(-/-) mice successfully prevented formation of cysts in the brain. However, transfer of naïve CD8(+) T cells from WT into STAT6(-/-) mice did not show either activation of CD8(+) T cells or a decrease in the number of cysts in the brain. Transfer of splenic adherent cells from WT into STAT6(-/-) mice induced activation of CD8(+) T cells and decreased the number of cysts in the brain. Expression of CD86 on splenic dendritic cells and IL-12 p40 production were weaker in STAT6(-/-) than in WT mice after T. gondii infection. These results indicate that STAT6 signalling is important in CD8(+) T-cell activation, possibly through regulation of antigen-presenting cells, which could suppress T. gondii infection in the brain.
Jin
Donghao
D
Department of Infection and Host Defence, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
Takamoto
Masaya
M
Hu
Tao
T
Taki
Shinsuke
S
Sugane
Kazuo
K
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002478:Cells, Cultured; D007371:Interferon-gamma / Q000096:biosynthesis / Q000134:cerebrospinal fluid; D008213:Lymphocyte Activation / Q000276:immunology; D017710:Lymphocyte Transfusion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050800:STAT6 Transcription Factor / Q000172:deficiency / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000276:immunology / Q000469:parasitology / Q000473:pathology / Q000517:prevention & control; D016781:Toxoplasmosis, Cerebral / Q000276:immunology* / Q000469:parasitology / Q000473:pathology / Q000517:prevention & control
D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D007371:Interferon-gamma
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