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首页> 外文期刊>Infection and immunity >Protective Toxoplasma gondii-Specific T-Cell Responses Require T-Cell-Specific Expression of Protein Kinase C-Theta
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Protective Toxoplasma gondii-Specific T-Cell Responses Require T-Cell-Specific Expression of Protein Kinase C-Theta

机译：保护性弓形虫特异性T细胞反应需要蛋白激酶C-Theta的T细胞特异性表达

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Protein kinase C-theta (PKC-θ) is important for the activation of autoreactive T cells but is thought to be of minor importance for T-cell responses in infectious diseases, suggesting that PKC-θ may be a target for the treatment of T-cell-mediated autoimmune diseases. To explore the function of PKC-θ in a chronic persisting infection in which T cells are crucial for pathogen control, we infected BALB/c PKC-θ?/? and PKC-θ+/+ wild-type mice with Toxoplasma gondii. The PKC-θ?/? mice succumbed to necrotizing Toxoplasma encephalitis due to an insufficient parasite control up to day 40, whereas the wild-type mice survived. The number of T. gondii-specific CD4 and CD8 T cells was significantly reduced in the PKC-θ?/? mice, resulting in the impaired production of protective cytokines (gamma interferon, tumor necrosis factor) and antiparasitic effector molecules (inducible nitric oxide, gamma interferon-induced GTPase) in the spleen and brain. In addition, Th2-cell numbers were reduced in infected the PKC-θ?/? mice, paralleled by the diminished GATA3 expression of PKC-θ?/? CD4 T cells and reduced T. gondii-specific IgG production in serum and cerebrospinal fluid. Western blot analysis of splenic CD4 and CD8 T cells revealed an impaired activation of the NF-κB, AP-1, and MAPK pathways in T. gondii-infected PKC-θ?/? mice. Adoptive transfer of wild-type CD4 plus CD8 T cells significantly protected PKC-θ?/? mice from death by increasing the numbers of gamma interferon-producing T. gondii-specific CD4 and CD8 T cells, illustrating a cell-autonomous, protective function of PKC-θ in T cells. These findings imply that PKC-θ inhibition drastically impairs T. gondii-specific T-cell responses with fatal consequences for intracerebral parasite control and survival.
机译：蛋白激酶C-θ（PKC-θ）对于激活自身反应性T细胞很重要，但对感染性疾病中T细胞反应的重要性次之，这表明PKC-θ可能是治疗T的靶标细胞介导的自身免疫性疾病。为了探索PKC-θ在T细胞对病原体控制至关重要的慢性持续感染中的功能，我们感染了BALB / cPKC-θ？/？和PKC-θ + / + 弓形虫弓形虫的野生型小鼠。直到第40天，由于寄生虫控制不足，PKC-θ？/？小鼠死于坏死性弓形虫性脑炎。 T的数量。在PKC-θ？/？小鼠中，弓形虫特异的CD4和CD8 T细胞显着减少，导致保护性细胞因子（γ干扰素，肿瘤坏死因子）的产生受损和抗寄生虫脾脏和大脑中的效应分子（诱导型一氧化氮，γ干扰素诱导的GTP酶）。此外，感染的PKC-θ？/？小鼠中的Th2细胞数减少，同时PKC-θ？/？ CD4 T细胞的GATA3表达降低。并降低了 T。血清和脑脊液中产生刚地菌特异性IgG。脾脏CD4和CD8 T细胞的Western印迹分析显示， T中NF-κB，AP-1和MAPK通路的激活受损。刚地感染的PKC-θ？/？小鼠。野生型CD4 + CD8 T细胞的过继转移通过增加产生γ干扰素的 T的数量，显着保护了PKC-θ？/？小鼠免于死亡。刚地特异的CD4和CD8 T细胞，说明T细胞中PKC-θ具有细胞自主保护功能。这些发现暗示PKC-θ抑制作用极大地损害了T。弓形虫特异的T细胞反应，对脑内寄生虫的控制和存活具有致命的后果。

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