Mount Jeremy A, Karrow Niel A, Caswell Jeff L, Boermans Herman J, Leslie Ken E
Center for Genetic Improvement of Livestock, Department of Animal and Poultry Science, University of Guelph, Ontario, Canada.
Can J Vet Res. 2009 Jan;73(1):49-57.
During intramammary infections pathogen associated molecular patterns (PAMPs) induce an inflammatory response, recognized clinically as mastitis. Recognition of PAMPs by mammary cells leads to the production of the pro-inflammatory cytokines, TNF-alpha and IL-1beta. These cytokines augment the secretion of various chemokines that are responsible for directing the host cellular immune response, and consequently the outcome of infection. Previous research has shown that gram-negative and gram-positive bacteria elicit different types of innate immune responses. The purpose of this study, therefore, was to characterize the expression of various chemokine genes in bovine mammary gland explants in response to lipopolysaccharide (LPS), peptidoglycan (PTG) combined with lipotechoic acid (LTA), and CpG oligodeoxynucleotide (CpG-ODN) 2135 representing gram-negative bacteria, gram-positive bacteria, and bacterial DNA, respectively, to determine if these PAMPs induce different chemokine gene expression patterns. Explants from 3 Holstein cows were cultured with 10 microg/mL of LPS, LTA + PTG, or CpG-ODN 2135 for 6 and 24 h. Total RNA was extracted and the expression of CXCL8, MCP-1, MCP-2, MCP-3, MIP1-alpha, and RANTES genes was measured by real-time polymerase chain reaction (RT-PCR). Lipopolysaccharide significantly induced MCP-1, MCP-2, and MCP-3 expression, and slightly increased CXCL8 gene expression. The combined PAMPs, LTA + PTG, on the other hand, significantly induced MCP-1 gene expression, and slightly increased MCP-3 expression. No significant expression differences for any of the chemokine genes were observed in explants stimulated with CpG-ODN 2135. These results demonstrate that PAMPs associated with different mastitis-causing pathogens induce chemokine-specific gene expression patterns that may contribute to different innate immune responses to bacteria.
在乳房内感染期间,病原体相关分子模式(PAMPs)会引发炎症反应,临床上表现为乳腺炎。乳腺细胞对PAMPs的识别会导致促炎细胞因子肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)的产生。这些细胞因子会增加各种趋化因子的分泌,而趋化因子负责引导宿主细胞免疫反应,进而影响感染的结果。先前的研究表明,革兰氏阴性菌和革兰氏阳性菌会引发不同类型的先天免疫反应。因此,本研究的目的是表征牛乳腺外植体中各种趋化因子基因在分别响应代表革兰氏阴性菌的脂多糖(LPS)、结合脂磷壁酸(LTA)的肽聚糖(PTG)以及细菌DNA的CpG寡脱氧核苷酸(CpG-ODN)2135时的表达情况,以确定这些PAMPs是否会诱导不同的趋化因子基因表达模式。从3头荷斯坦奶牛获取的外植体用10微克/毫升的LPS、LTA + PTG或CpG-ODN 2135培养6小时和24小时。提取总RNA,并通过实时聚合酶链反应(RT-PCR)测量CXCL8、MCP-1、MCP-2、MCP-3、MIP1-α和RANTES基因的表达。脂多糖显著诱导MCP-1、MCP-2和MCP-3的表达,并略微增加CXCL8基因的表达。另一方面,组合的PAMPs,即LTA + PTG,显著诱导MCP-1基因的表达,并略微增加MCP-3的表达。在用CpG-ODN 2135刺激的外植体中,未观察到任何趋化因子基因有显著的表达差异。这些结果表明,与不同乳腺炎致病病原体相关的PAMPs会诱导趋化因子特异性基因表达模式,这可能导致对细菌的先天免疫反应有所不同。