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首页> 外文期刊>Infection and immunity >The Protozoan Neospora caninum Directly Triggers Bovine NK Cells To Produce Gamma Interferon and To Kill Infected Fibroblasts
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The Protozoan Neospora caninum Directly Triggers Bovine NK Cells To Produce Gamma Interferon and To Kill Infected Fibroblasts

机译：原生动物新孢子虫可直接触发牛NK细胞产生γ干扰素并杀死感染的成纤维细胞。

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Natural killer (NK) cells are considered to be key players in the early innate responses to protozoan infections, primarily indirectly by producing gamma interferon (IFN-γ) in response to cytokines, like interleukin 12 (IL-12). We demonstrate that live, as well as heat-inactivated, tachyzoites of Neospora caninum, a Toxoplasma-like protozoan, directly trigger production of IFN-γ from purified, IL-2-activated bovine NK cells. This response occurred independently of IL-12 but was increased by the addition of the cytokine. A similar IFN-γ response was measured in cocultures of NK cells and N. caninum-infected autologous fibroblasts. However, no NK cell-derived IFN-γ response was detected when cells were cultured with soluble antigens from the organism, indicating that intact tachyzoites or nonsoluble components are necessary for NK cell triggering. Furthermore, N. caninum-infected autologous fibroblasts had increased susceptibility to NK cell cytotoxicity compared to uninfected fibroblasts. This cytotoxicity was largely mediated by a perforin-mediated mechanism. The activating receptor NKp46 was involved in cytotoxicity against fibroblasts but could not explain the increased cytotoxicity against infected targets. Interestingly, N. caninum tachyzoites were able to infect cultured NK cells, in which tachyzoites proliferated inside parasitophorous vacuoles. Together, these findings underscore the role of NK cells as primary responders during a protozoan infection, describe intracellular protozoan infection of NK cells in vitro for the first time, and represent the first functional study of purified bovine NK cells in response to infection.
机译：天然杀伤（NK）细胞被认为是对原生动物感染的早期先天反应的关键参与者，主要是通过对细胞因子（如白介素12（IL-12））的反应产生γ干扰素（IFN-γ）而间接产生这种作用。我们证明了新孢子虫（一种弓形虫类原生动物）的活的以及热灭活的速殖子直接触发了纯化的IL-2的IFN-γ产生。激活的牛NK细胞。该反应独立于IL-12而发生，但是通过添加细胞因子而增加。在NK细胞和 N的共培养物中测量到类似的IFN-γ应答。犬感染的自体成纤维细胞。但是，当用来自生物体的可溶性抗原培养细胞时，未检测到源自NK细胞的IFN-γ反应，这表明完整的速殖子或不溶性成分对于NK细胞触发是必需的。此外， N。与未感染的成纤维细胞相比，犬感染的自体成纤维细胞对NK细胞毒性的敏感性增加。这种细胞毒性主要由穿孔素介导的机制介导。激活受体NKp46参与了针对成纤维细胞的细胞毒性作用，但不能解释针对感染目标的增加的细胞毒性作用。有趣的是， N。犬速殖子能够感染培养的NK细胞，其中速殖子在寄生虫的液泡内增殖。总之，这些发现强调了NK细胞在原生动物感染期间作为主要应答者的作用，首次描述了NK细胞在细胞内的原生动物感染，并且首次代表了纯化牛NK细胞对感染的反应。

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