Bacterial Burden Declines But Neutrophil Infiltration and Ocular Tissue Damage Persist in Experimental Staphylococcus epidermidis Endophthalmitis.
Bacterial Burden Declines But Neutrophil Infiltration and Ocular Tissue Damage Persist in Experimental Staphylococcus epidermidis Endophthalmitis.
复制标题
DOI：
10.3389/fcimb.2021.780648
复制
发表时间：
2021
影响因子：
5.7
通讯作者：
Kumar A
中科院分区：
文献类型：
--
作者：
Das S;Singh S;Kumar A
凝固酶阴性葡萄球菌 (CoNS)，包括表皮葡萄球菌 (S)，导致约 70% 的术后眼内炎，这是一种可能致盲的眼部感染。然而，CoNS眼内炎的病理学仅限于流行病学和临床病例研究，实验研究很少。在这里，我们报告了体外和体内模型来研究小鼠表皮葡萄球菌眼内炎的病理学。 我们发现表皮葡萄球菌能迅速从小鼠眼中清除，并且需要相对较高的剂量（即 107 CFU/眼）才能引起眼内炎。我们的时间进程研究表明，细菌负荷在感染后 24 小时达到峰值，随后逐渐下降，直至 72 小时。炎症介质水平和 Toll 样受体 (TLR) 表达也观察到类似的时间依赖性下降。相比之下，中性粒细胞浸润持续增加长达 72 小时，同时出现明显的视网膜组织损伤和视功能丧失。在体外，表皮葡萄球菌诱导多种炎症信号通路（即 NF-kB、ERK 和 P38）的激活以及小鼠 BMDM、人 RPE 和视网膜 Muller 胶质细胞中细胞因子和趋化因子的产生。总而言之，我们表明表皮葡萄球菌眼内炎的细菌负荷减少，而组织损伤和视觉功能丧失仍在继续。因此，我们的研究为 CoNS 眼内炎的发病机制提供了新的见解。
Coagulase-negative staphylococci (CoNS), including Staphylococcus (S) epidermidis, are responsible for ~70% of all post-surgical endophthalmitis, a potentially blinding eye infection. However, the pathobiology of CoNS endophthalmitis is limited to epidemiological and clinical case studies with few experimental studies. Here, we report both in vitro and in vivo models to study the pathobiology of S. epidermidis endophthalmitis in mice. We found that S. epidermidis is rapidly cleared from mouse eyes, and a relatively higher dose (i.e., 107 CFU/eye) was needed to cause endophthalmitis. Our time-course study revealed that bacterial load peaked at 24 h post-infection followed by a gradual decline up to 72 h. A similar time-dependent decrease in levels of inflammatory mediators and Toll-like receptor (TLR) expression was also observed. In contrast, neutrophil infiltration continued to increase up to 72 h coinciding with significant retinal tissue damage and loss of visual function. In vitro, S. epidermidis induced the activation of various inflammatory signaling pathways (i.e., NF-kB, ERK, and P38) and the production of both cytokines and chemokines in mouse BMDMs, human RPE, and retinal Muller glia. Altogether, we show that bacterial burden is reduced in S. epidermidis endophthalmitis, while tissue damage and visual function loss continue. Thus, our study provides new insights into the pathogenesis of CoNS endophthalmitis.