Schistosoma mansoni-infected mice show augmented hepatic fibrosis and selective inhibition of liver cytokine production after treatment with anti-NK1.1 antibodies
Schistosoma mansoni-infected mice show augmented hepatic fibrosis and selective inhibition of liver cytokine production after treatment with anti-NK1.1 antibodies
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DOI：
10.1016/s0165-2478(96)02634-x
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发表时间：
1996-12-01
影响因子：
4.4
通讯作者：
Auriault, C
中科院分区：
文献类型：
--
作者：
Asseman, C;Pancre, V;Auriault, C
γ干扰素（IFN-γ）通过其诱导细胞对寄生虫幼虫的细胞毒性和减少已建立的肝纤维化的能力，在小鼠中实验性曼氏血吸虫驱动过程的不同阶段发挥免疫调节作用。自然杀伤（NK）细胞作为IFN-γ的可能主要来源，在小鼠血吸虫病的整个过程中的作用从未被研究过。在本文中，我们研究了感染17周期间维持的体内NK细胞耗竭对肝肉芽肿发展和免疫学参数的影响。我们发现，抗NK1.1单克隆抗体（mAb）注射后NK细胞耗竭导致肉芽肿形成后期肝脏胶原含量增加，肝脏中白细胞介素12（IL-12）p40和IL-7 mRNA表达减少。其它细胞因子（IFN-γ、肿瘤坏死因子α [TNF-α]和IL-4）的肝脏mRNA表达以及血清中的体液和细胞因子应答在对照单克隆抗体（CmAb）和抗NK1.1处理的小鼠之间没有显著差异。因此，我们证明，抗NK1.1治疗可能会引起调节机制的改变，在免疫活性小鼠的慢性过程的后期阶段检测。版权所有（C）1996 Elsevier Science B. V.
Gamma interferon (IFN-gamma) plays an immunoregulatory role at different stages of the experimental Schistosoma mansoni-driven processes in mice through its ability to induce cell cytotoxicity against the parasite larvae and to reduce established hepatic fibrosis. The role of Natural Killer (NK) cells, as a possible major source of IFN-gamma, has never been studied during the entire course of murine schistosomiasis. In this paper, we investigated the consequences of in vivo NK cell depletion, maintained during 17 weeks of infection, on both hepatic granuloma development and immunological parameters. We found that NK cell depletion following anti-NK1.1 monoclonal antibody (mAb) injections led to an increase of hepatic collagen content in the late stages of granuloma formation and to the diminution of interleukin 12 (IL-12) p40 and IL-7 mRNA expression in the livers. The hepatic mRNA expression of other cytokines (IFN-gamma, tumor necrosis factor alpha [TNF-alpha] and IL-4), as well as humoral and cytokine responses in sera, were not significantly different between control monoclonal antibody (CmAb) and anti-NK1.1-treated mice. Thus, we demonstrate that the anti-NK1.1 treatment might induce alterations of regulatory mechanisms, detectable at a late stage of a chronic process in immunocompetent mice. Copyright (C) 1996 Elsevier Science B.V.