Subharat Supatsak, Shu Dairu, de Lisle Geoffrey W, Buddle Bryce M, Wedlock D Neil
AgResearch, Hopkirk Research Institute, Grasslands Research Centre, Private Bag 11008, Palmerston North 4442, New Zealand.
Vet Immunol Immunopathol. 2012 Jan 15;145(1-2):471-8. doi: 10.1016/j.vetimm.2011.10.008. Epub 2011 Oct 21.
Johne's disease caused by Mycobacterium avium subsp. paratuberculosis (MAP), is a chronic enteric disease of cattle. The mechanism how MAP can co-exist in the gastro-intestinal tract despite a massive infiltration of immune cells is not known. Toll-like receptors (TLRs) are known to play an important role in both innate and acquired immune responses but it is unclear what role different TLRs play in response to MAP. In this study, 38 cull cows from herds infected with MAP were classified into four groups, based on MAP culture from gut tissues and histopathological lesion scores. The expression of TLR1, 2 and 4 mRNA from MAP antigen-stimulated mesenteric lymph node (MLN) cultures and peripheral blood mononuclear cells (PBMCs) and in the MLN and ileum tissues of these animals was determined. MAP antigen-specific expression of TLR1 in MLN and PBMC was significantly lower in the MAP-infected groups than the non-infected control group, suggesting that in MAP-infected animals there is impairment in the up-regulation of TLR1 in response to MAP antigen. TLR4 expression in MLN tissues was significantly higher in the severely infected group than the control group suggesting up-regulation of endogenous TLR4 expression at a site of MAP infection in animals severely affected with Johne's disease. A preliminary screening of TLR1, 2 and 4 in the cull cows revealed the presence of polymorphisms in TLR1 and TLR2. In summary, one mechanism how MAP may subvert the immune system is that there is an apparent lack of recognition of MAP antigens as foreign by TLR1 in MAP-infected cows.
由副结核分枝杆菌（MAP）引起的副结核病是牛的一种慢性肠道疾病。尽管有大量免疫细胞浸润，MAP如何在胃肠道中共存的机制尚不清楚。已知Toll样受体（TLR）在先天性和获得性免疫反应中都发挥着重要作用，但不同的TLR在对MAP的反应中起什么作用尚不清楚。在本研究中，根据肠道组织的MAP培养和组织病理学病变评分，将38头来自感染MAP牛群的淘汰母牛分为四组。测定了MAP抗原刺激的肠系膜淋巴结（MLN）培养物和外周血单核细胞（PBMC）以及这些动物的MLN和回肠组织中TLR1、2和4 mRNA的表达。MAP感染组中MLN和PBMC中TLR1的MAP抗原特异性表达明显低于未感染的对照组，这表明在MAP感染的动物中，对MAP抗原的反应中TLR1的上调存在损害。严重感染组MLN组织中TLR4的表达明显高于对照组，这表明在患有严重副结核病的动物中，MAP感染部位的内源性TLR4表达上调。对淘汰母牛中TLR1、2和4的初步筛选显示TLR1和TLR2存在多态性。总之，MAP可能颠覆免疫系统的一种机制是，在MAP感染的奶牛中，TLR1明显缺乏将MAP抗原识别为外来抗原的能力。
