Effect of stress on viral-bacterial synergy in bovine respiratory disease: novel mechanisms to regulate inflammation.
Effect of stress on viral-bacterial synergy in bovine respiratory disease: novel mechanisms to regulate inflammation.
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DOI：
10.1002/cfg.474
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发表时间：
2005
影响因子：
--
通讯作者：
Griebel, P J
中科院分区：
文献类型：
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作者：
Hodgson, P D;Aich, P;Manuja, A;Hokamp, K;Roche, F M;Brinkman, F S L;Potter, A;Babiuk, L A;Griebel, P J
牛呼吸道感染的严重程度与多种因素有关，包括环境和营养变化、运输和断奶小牛的社会重组。然而，致命的呼吸道感染通常发生在原发性病毒感染损害宿主防御并增强继发性细菌感染的严重性时。这种病毒-细菌协同作用可以通过许多不同的机制发生，并且已经开发了疾病挑战模型来分析这些呼吸道感染期间的宿主反应。牛疱疹病毒1型（BHV-1）的原发性呼吸道感染，随后用溶血性曼氏菌进行二次攻毒，可导致致死性牛呼吸道疾病（BRD），宿主对这两种病原体的反应已被广泛研究。我们使用这种疾病模型来证明，压力显着改变了病毒-细菌的协同作用，导致致命的BRD。功能基因组分析显示，BHV-1感染增强了Toll样受体（TLR）的表达，并增加了促炎反应，这有助于溶血性曼氏菌感染的严重程度。TLR在检测细菌感染和诱导促炎反应中起关键作用。然而，很难理解应激诱导的皮质类固醇如何增强这种形式的病毒-细菌协同作用。糖皮质激素受体的核转位激活细胞信号传导途径，其抑制TLR信号传导和促炎反应。压力诱导的皮质类固醇和增强BRD的易感性之间的明显的难题进行了讨论，目前的数据和以前的调查压力和呼吸系统疾病。
The severity of bovine respiratory infections has been linked to a variety of factors, including environmental and nutritional changes, transportation, and social reorganization of weaned calves. Fatal respiratory infections, however, usually occur when a primary viral infection compromises host defences and enhances the severity of a secondary bacterial infection. This viral–bacterial synergy can occur by a number of different mechanisms and disease challenge models have been developed to analyse host responses during these respiratory infections. A primary bovine herpesvirus-1 (BHV-1) respiratory infection followed by a secondary challenge with Mannheimia haemolytica results in fatal bovine respiratory disease (BRD) and host responses to these two pathogens have been studied extensively. We used this disease model to demonstrate that stress significantly altered the viral–bacterial synergy resulting in fatal BRD. Functional genomic analysis revealed that BHV-1 infection enhanced toll-like receptors (TLR) expression and increased pro-inflammatory responses which contribute to the severity of a Mannheimia haemolytica infection. TLRs play a critical role in detecting bacterial infections and inducing pro-inflammatory responses. It is difficult to understand, however, how stress-induced corticosteroids could enhance this form of viral–bacterial synergy. Nuclear translocation of the glucocorticoid receptor activates cell signalling pathways which inhibit both TLR signalling and pro-inflammatory responses. The apparent conundrum between stress-induced corticosteroids and enhanced BRD susceptibility is discussed in terms of present data and previous investigations of stress and respiratory disease.