Lipopolysaccharide pretreatment of the udder protects against experimental Escherichia coli mastitis
Lipopolysaccharide pretreatment of the udder protects against experimental Escherichia coli mastitis
复制标题
DOI：
10.1177/1753425911422407
复制
发表时间：
2012-06-01
期刊：
影响因子：
3.2
通讯作者：
Zerbe, Holm
中科院分区：
文献类型：
--
作者：
Petzl, Wolfram;Guenther, Juliane;Zerbe, Holm
暴露于病原体相关的分子模式如LPS可在哺乳动物中引起称为内毒素耐受性（ET）的免疫不应状态，导致病原体接触后炎症反应降低。该ET概念用于降低实验诱导的临床乳腺炎的严重程度。用1 μ g LPS/乳区预处理奶牛，72 h（L72 EC组）或240 h（L240 EC组）后用500 CFU大肠杆菌攻毒。与未经预处理的奶牛相比，经预处理的动物在攻毒后未显示白细胞减少症，体温未升高（L72 EC）或仅轻微升高（L240 EC），全身和局部临床评分显著降低。而E. L72 EC组动物的大肠杆菌攻击被取消，L240 EC组动物的攻击被显著延迟。在两个预处理组中，牛奶中的细菌负荷显著降低。基于小叶-肺泡乳腺组织中炎症相关基因的表达，LPS预处理的耐受作用是基于抑制炎症基因（TNF-α、IL-6、CXCL 8、CCL 20）和抗炎基因（IL-10、IRAK-M）的上调。这些研究结果表明，ET的概念可以有效地应用于乳腺炎预防，促进对微生物感染的快速反应，避免失调的炎症。
Exposure to pathogen-associated molecular patterns such as LPS can cause an immune refractory state in mammals known as endotoxin tolerance (ET), resulting in a decreased inflammatory response after pathogen contact. This ET concept was used to reduce the severity of an experimentally-induced clinical mastitis. Cows were pretreated with 1 mu g LPS per udder quarter and challenged 72 h (group L72EC) or 240 h (group L240EC) later with 500 CFU Escherichia coli. Pretreated animals showed no leukopenia after challenge, no (L72EC), or only slightly (L240EC), elevated body temperature and significantly reduced systemic and local clinical scores compared with cows that were not pretreated. Whereas an increase of milk somatic cell count after the E. coli challenge was abrogated in L72EC animals, it was significantly delayed in the L240EC group. In both pretreated groups the bacterial load in milk was markedly reduced. Based on the expression of inflammation-related genes in lobulo-alveolar mammary tissue, the tolerizing effect of LPS pretreatment is based on the inhibited up-regulation of inflammatory (TNF-alpha, IL-6, CXCL8, CCL20) and anti-inflammatory genes (IL-10, IRAK-M). These findings indicate that the concept of ET may be usefully applied as mastitis prophylaxis facilitating a rapid response to microbial infection and avoiding dysregulated inflammation.