Regulation of Trypanosoma cruzi infection in mice by gamma interferon and interleukin 10: Role of NK cells
Regulation of Trypanosoma cruzi infection in mice by gamma interferon and interleukin 10: Role of NK cells
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DOI：
10.1128/iai.64.1.128-134.1996
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发表时间：
1996-01-01
影响因子：
3.1
通讯作者：
Silva, JS
中科院分区：
文献类型：
--
作者：
Cardillo, F;Voltarelli, JC;Silva, JS
干扰素在实验性克氏锥虫感染中起重要作用，可能是通过控制宿主巨噬细胞中寄生虫的早期复制。在这项工作中，我们证明了NK细胞代表着一种重要的细胞类型，在克氏锥虫感染的早期阶段，NK细胞是产生大部分干扰素-伽马的重要细胞类型，并且体内用抗NK1.1单抗治疗小鼠使耐药动物对感染易感。通过体外实验，我们证明了用克氏锥虫活体培养48h后，胸腺或无胸腺裸鼠的正常脾细胞产生高水平的干扰素-γ。此外，NK耗尽的脾细胞表现出对活的克氏锥虫的反应，干扰素-γ的产生急剧减少。裸鼠脾细胞培养上清液能诱导正常脾细胞产生干扰素-γ，加入抗白细胞介素10可显著增加培养物中干扰素-γ的产生。另一方面，NK细胞的缺失导致克氏毛滴虫体外刺激时IL-10的分泌增加。综上所述，这些结果表明，NK细胞是干扰素-γ的主要来源，在感染的早期急性阶段，NK细胞可能参与限制宿主巨噬细胞中克氏锥虫的复制。
Gamma interferon (IFN-gamma) plays an important role in experimental Trypanosoma cruzi infections, presumably by controlling the early replication of parasites in host macrophages, In this work we show that NK cells represent an important cell type responsible for the production of most of the IFN-gamma in the early stages of T. cruzi infection and that the in vivo treatment of mice with anti-NK1.1 monoclonal antibody made resistant animals susceptible to the infection. Through in vitro experiments, we demonstrate that normal splenocytes from euthymic or athymic nude mice cultivated for 48 h with live T. cruzi trypomastigotes produced elevated levels of IFN-gamma. In addition, NK-depleted splenocytes show a drastic reduction of IFN-gamma production in response to live T. cruzi trypomastigotes. We also demonstrate that IFN-gamma production is dependent on a factor secreted by adherent cells, Supernatants of spleen cells from athymic nude mice are able to induce IFN-gamma production by normal splenocytes when cultured with trypomastigotes, The addition of anti-interleukin-10 to these cultures resulted in a marked increase in IFN-gamma production. On the other hand, the absence of NK cells led to an increased secretion of interleukin-10 upon in vitro stimulation with T. cruzi. Taken together, these results suggest that NK cells are the major source of IFN-gamma that could he involved in limiting the replication of T. cruzi in host macrophages during the early acute phase of the infection.