Control of Methicillin-Resistant Staphylococcus aureus Pneumonia Utilizing TLR2 Agonist Pam3CSK4.
Control of Methicillin-Resistant Staphylococcus aureus Pneumonia Utilizing TLR2 Agonist Pam3CSK4.
复制标题
利用 TLR2 激动剂 Pam3CSK4 控制耐甲氧西林金黄色葡萄球菌肺炎。
DOI：
10.1371/journal.pone.0149233
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Min WP
中科院分区：
文献类型：
--
作者：
Chen YG;Zhang Y;Deng LQ;Chen H;Zhang YJ;Zhou NJ;Yuan K;Yu LZ;Xiong ZH;Gui XM;Yu YR;Wu XM;Min WP
耐甲氧西林金黄色葡萄球菌（MRSA）的传播是一个关键的健康问题，引起了人们对免疫疗法潜在用途的更多关注。Toll样受体2（TLR 2）是一种模式识别受体，是宿主天然防御系统的重要组成部分。金黄色葡萄球菌感染。然而，人们对针对MRSA感染的先天免疫反应（特别是TLR 2激活）知之甚少。在这里，我们评估了TLR 2激动剂Pam 3CSK 4预处理后对MRSA小鼠肺炎的保护作用和机制。我们发现，与对照小鼠相比，用Pam 3CSK 4预处理的MRSA-肺炎小鼠模型具有减少的细菌和死亡率。Pam 3CSK 4预处理组肺和支气管中TNF-α、IL-1β和IL-6的蛋白和mRNA水平较低。相反，在Pam 3CSK 4预处理的小鼠中，抗炎细胞因子IL-10的表达增加，但TGF-β没有增加。我们的进一步研究表明，与对照组相比，Pam 3CSK 4预处理组中中性粒细胞募集所必需的CXCL-2和CXCL 1较不明显，而小鼠肺中Fcγ受体（FcγⅠ/Ⅲ）和补体受体（CR 1/3）的表达增加。此外，我们发现增加的存活率和改善的细菌清除率不是较高水平的中性粒细胞浸润的结果，而是体外和体内中性粒细胞的吞噬作用和杀菌活性增强以及乳铁蛋白的稳健氧化活性和释放增加的结果。我们的累积研究结果表明，Pam 3CSK 4可能是一种新的抗MRSA肺炎的免疫候选物。
The spread of methicillin-resistant Staphylococcus aureus (MRSA) is a critical health issue that has drawn greater attention to the potential use of immunotherapy. Toll-like receptor 2 (TLR2), a pattern recognition receptor, is an essential component in host innate defense system against S. aureus infection. However, little is known about the innate immune response, specifically TLR2 activation, against MRSA infection. Here, we evaluate the protective effect and the mechanism of MRSA murine pneumonia after pretreatment with Pam3CSK4, a TLR2 agonist. We found that the MRSA-pneumonia mouse model, pretreated with Pam3CSK4, had reduced bacteria and mortality in comparison to control mice. As well, lower protein and mRNA levels of TNF-α, IL-1β and IL-6 were observed in lungs and bronchus of the Pam3CSK4 pretreatment group. Conversely, expression of anti-inflammatory cytokine IL-10, but not TGF-β, increased in Pam3CSK4-pretreated mice. Our additional studies showed that CXCL-2 and CXCL1, which are necessary for neutrophil recruitment, were less evident in the Pam3CSK4-pretreated group compared to control group, whereas the expression of Fcγ receptors (FcγⅠ/Ⅲ) and complement receptors (CR1/3) increased in murine lungs. Furthermore, we found that increased survival and improved bacterial clearance were not a result of higher levels of neutrophil infiltration, but rather a result of enhanced phagocytosis and bactericidal activity of neutrophils in vitro and in vivo as well as increased robust oxidative activity and release of lactoferrin. Our cumulative findings suggest that Pam3CSK4 could be a novel immunotherapeutic candidate against MRSA pneumonia.