Comparative Genomics Centre, James Cook University, Townsville, Australia.
Int J Parasitol. 2010 Jul;40(8):879-88. doi: 10.1016/j.ijpara.2010.03.011. Epub 2010 Apr 24.
The inhibition of TNF with therapeutic monoclonal antibodies or antibody/receptor fusion proteins in rheumatoid arthritis still constitutes the benchmark for a successful intervention in an ongoing auto-immune-inflammatory disease and underlines the importance of this cytokine. TNF plays a central role in the defence against intracellular infections and is responsible for the promotion of different aspects of the innate immune response such as inflammatory cell recruitment and cell differentiation. While this cytokine generally displays pro-inflammatory activities supporting the early stages of the inflammatory response, it has been demonstrated to be especially important during infection with intracellular pathogens and, consequently, leishmaniasis of TNF(-/-) mice ends fatally. However, the specific activities of TNF that confer protection are not yet fully understood. This review will summarize the current understanding of TNF function and signalling, and will discuss recent work in the models of malaria, toxoplasmosis, trypanosomiasis and leishmaniasis with particular emphasis on work with gene-deficient mouse models.
在类风湿关节炎中，使用治疗性单克隆抗体或抗体/受体融合蛋白抑制 TNF 仍然是成功干预正在进行的自身免疫性炎症性疾病的基准，突显了这种细胞因子的重要性。TNF 在抵抗细胞内感染中发挥核心作用，并负责促进先天免疫反应的不同方面，如炎症细胞募集和细胞分化。虽然这种细胞因子通常表现出促炎活性，支持炎症反应的早期阶段，但已证明它在细胞内病原体感染期间特别重要，因此 TNF(-/-) 小鼠的利什曼病最终致命。然而，赋予保护作用的 TNF 的具体活性尚未完全了解。这篇综述将总结 TNF 功能和信号转导的最新认识，并将讨论疟疾、弓形虫病、锥虫病和利什曼病模型中的最新工作，特别强调基因缺失小鼠模型的工作。
