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乳头瘤状指皮炎螺旋体抑制牛巨噬细胞的先天性免疫反应。

Papillomatous digital dermatitis spirochetes suppress the bovine macrophage innate immune response.

作者信息

Zuerner Richard L, Heidari Mohammad, Elliott Margaret K, Alt David P, Neill John D

机构信息

Bacterial Diseases of Livestock Research Unit, National Animal Disease Center, USDA, ARS, Ames, IA 50010, USA.

出版信息

Vet Microbiol. 2007 Dec 15;125(3-4):256-64. doi: 10.1016/j.vetmic.2007.06.001. Epub 2007 Jun 13.

DOI:10.1016/j.vetmic.2007.06.001
PMID:17628359
Abstract

Papillomatous digital dermatitis (PDD) is a polymicrobial infection in soft tissue adjacent to the hoof and is the leading cause of lameness in dairy cattle. Treponema phagedenis-like (TPL) spirochetes are a constant feature of PDD lesions and are localized deep in infected tissue. Host-cell response mechanisms to TPL spirochetes are poorly understood. To assess how bovine macrophages respond to cellular constituents of TPL spirochetes, changes in transcription were analyzed using serial analysis of gene expression (SAGE) and real time RT-PCR. This analysis revealed that some proinflammatory cytokines (e.g. GCP-2 and IL-8) are induced in treated macrophages, while receptors and their accessory proteins for IL-1, IL-6 and IL-11 are either down regulated or unchanged. Two genes encoding proteins having negative effects on NFkappaB, IkappaB and SIVA-1, are significantly induced in stimulated cells. Several genes associated with the cytoskeleton and antigen presentation are down regulated after exposure to sonicated TPL spirochetes, as are genes associated with wound repair. Combined, these data suggest that the innate immune and wound repair functions of bovine macrophages exposed to TPL cellular constituents are impaired thereby enabling bacteria to resist clearance and induce lesion formation. Use of this in vitro bovine macrophage model should be useful in elucidating host-spirochete interactions and facilitate identification of potential virulence traits.

摘要

乳头瘤状趾间皮炎(PDD)是一种发生于蹄部附近软组织的多微生物感染,是奶牛跛行的主要原因。噬菌密螺旋体样(TPL)螺旋体是PDD病变的一个持续特征,定位于感染组织深部。宿主细胞对TPL螺旋体的反应机制尚不清楚。为了评估牛巨噬细胞如何对TPL螺旋体的细胞成分作出反应,利用基因表达序列分析(SAGE)和实时RT-PCR分析转录变化。该分析表明,在处理过的巨噬细胞中一些促炎细胞因子(如GCP-2和IL-8)被诱导,而IL-1、IL-6和IL-11的受体及其辅助蛋白要么下调要么不变。在受刺激的细胞中,编码对NFκB有负面影响的蛋白的两个基因,即IkappaB和SIVA-1,被显著诱导。暴露于超声处理的TPL螺旋体后,几个与细胞骨架和抗原呈递相关的基因以及与伤口修复相关的基因均下调。综合这些数据表明,暴露于TPL细胞成分的牛巨噬细胞的固有免疫和伤口修复功能受损,从而使细菌能够抵抗清除并诱导病变形成。使用这种体外牛巨噬细胞模型应有助于阐明宿主与螺旋体的相互作用,并促进潜在毒力特征的鉴定。

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