O'Gorman Grace M, Park Stephen D E, Hill Emmeline W, Meade Kieran G, Mitchell Laura C, Agaba Morris, Gibson John P, Hanotte Olivier, Naessens Jan, Kemp Stephen J, MacHugh David E
Animal Genomics Laboratory, School of Agriculture, Food Science and Veterinary Medicine, College of Life Sciences, University College Dublin, Belfield, Dublin, Ireland.
Physiol Genomics. 2006 Dec 13;28(1):53-61. doi: 10.1152/physiolgenomics.00100.2006. Epub 2006 Sep 19.
To examine differences in cytokine profiles that may confer tolerance/susceptibility to bovine African trypanosomiasis, N'Dama (trypanotolerant, n = 8) and Boran (trypanosusceptible, n = 8) cattle were experimentally challenged with Trypanosoma congolense. Blood samples were collected over a 34-day period, and RNA was extracted from peripheral blood mononuclear cells. The expression levels of a panel of 14 cytokines were profiled over the time course of infection and between breeds. Messenger RNA (mRNA) transcript levels for the IL2, IL8, and IL1RN genes were significantly downregulated across the time course of infection in both breeds. There was an early increase in transcripts for genes encoding proinflammatory mediators (IFNG, IL1A, TNF, and IL12) in N'Dama by 14 days postinfection (dpi) compared with preinfection levels that was not detected in the susceptible Boran breed. By the time of peak parasitemia, a type 2 helper T cells (T(H)2)-like cytokine environment was prevalent that was particularly evident in the Boran. Increases in transcripts for the IL6 (29 and 34 dpi) and IL10 (21, 25, and 29 dpi) genes were detected that were higher in the Boran compared with N'Dama. These findings highlight the implications for using murine models to study the bovine immune response to trypanosomiasis, where in some cases cytokine expression patterns differ. Overall, these data suggest that the trypanotolerant N'Dama are more capable of responding very early in infection with proinflammatory and T(H)1 type cytokines than the trypanosusceptible Boran and may explain why N'Dama control parasitemia more efficiently than Boran during the early stages of infection.
为研究可能赋予牛对非洲锥虫病耐受性/易感性的细胞因子谱差异，用刚果锥虫对N’Dama牛（锥虫耐受型，n = 8）和博拉纳牛（锥虫易感型，n = 8）进行实验性攻毒。在34天内采集血样，并从外周血单核细胞中提取RNA。在感染过程中及不同品种之间分析了一组14种细胞因子的表达水平。在两个品种的感染过程中，IL2、IL8和IL1RN基因的信使核糖核酸（mRNA）转录水平均显著下调。与感染前水平相比，N’Dama牛在感染后14天（dpi）时，编码促炎介质（IFNG、IL1A、TNF和IL12）的基因转录本早期增加，而在易感的博拉纳品种中未检测到这种增加。到寄生虫血症高峰期时，一种2型辅助性T细胞（T(H)2）样细胞因子环境普遍存在，在博拉纳牛中尤为明显。检测到IL6（29和34 dpi）和IL10（21、25和29 dpi）基因的转录本增加，博拉纳牛中的增加水平高于N’Dama牛。这些发现凸显了使用小鼠模型研究牛对锥虫病免疫反应的局限性，因为在某些情况下细胞因子表达模式存在差异。总体而言，这些数据表明，与易感的博拉纳牛相比，锥虫耐受型N’Dama牛在感染早期更能以促炎和T(H)1型细胞因子做出反应，这可能解释了为什么N’Dama牛在感染早期比博拉纳牛更有效地控制寄生虫血症。
