Toxoplasma gondii induces a T-independent IFN-gamma response in natural killer cells that requires both adherent accessory cells and tumor necrosis factor-alpha.
Toxoplasma gondii induces a T-independent IFN-gamma response in natural killer cells that requires both adherent accessory cells and tumor necrosis factor-alpha.
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弓形虫在自然杀伤细胞中诱导 T 细胞独立的 IFN-γ 反应，该反应需要粘附的辅助细胞和肿瘤坏死因子-α。
作者：
A. Sher;I. Oswald;S. Hieny;R. Gazzinelli
scid小鼠的脾细胞在暴露于弓形虫速殖子或可溶性寄生虫提取物时产生高水平的IFN-γ。少量的寄生虫就足以刺激这种反应，这也是诱导培养的速殖子的无细胞上清液。负责触发IFN-γ产生的寄生虫分子是热不稳定的，但耐冷冻和解冻。NK细胞或粘附细胞从脾细胞群中的消耗消除了应答。此外，培养的骨髓源性NK细胞被弓形虫刺激产生IFN-γ，但仅当补充有粘附的腹膜冲洗液或巯基乙酸盐诱导的渗出液细胞时。用T.刚地提取物还通过培养的NK细胞诱导IFN-γ合成。添加抗TNF-α的中和mAb可消除暴露于寄生虫的scid脾细胞或与T.弓形虫提取物此外，脾贴壁细胞产生低水平的TNF-α响应寄生虫。然而，单独的TNF-α不足以触发从纯化的NK细胞群体产生IFN-γ。这些发现提供了第一个例子，刺激T-非依赖性IFN-γ生产的原生动物。T.弓形虫感染触发这一途径可能是其诱导强烈的IFN-γ依赖的非特异性和特异性细胞介导的免疫的基础。
Spleen cells from scid mice produce high levels of IFN-gamma when exposed to either live tachyzoites of Toxoplasma gondii or a soluble parasite extract. Small numbers of parasites are sufficient to stimulate this response, which is also induced by cell-free supernatants of cultured tachyzoites. The parasite molecules responsible for triggering IFN-gamma production are heat-labile but resistant to freezing and thawing. Depletion of NK cells or adherent cells from the splenocyte population abolishes the response. Moreover, cultured bone marrow-derived NK cells are stimulated by Toxoplasma to produce IFN-gamma, but only when supplemented with adherent peritoneal washout or thioglycollate-induced exudate cells. Supernatants of macrophages preincubated with T. gondii extract also induce IFN-gamma synthesis by cultured NK cells. Addition of neutralizing mAb against TNF-alpha abolishes the IFN-gamma response of scid spleen cells exposed to the parasite or of NK cells incubated with supernatants of adherent cells stimulated with T. gondii extract. Moreover, splenic adherent cells produce low levels of TNF-alpha in response to the parasite. Nevertheless, TNF-alpha alone is not sufficient to trigger IFN-gamma production from purified NK cell populations. These findings provide the first example of the stimulation of T-independent IFN-gamma production by a protozoan. The ability of T. gondii to trigger this pathway may underlie its induction of strong IFN-gamma-dependent nonspecific and specific cell-mediated immunity.