Department of Ophthalmology, Visual and Anatomical Sciences/Kresge Eye Institute, Wayne State University School of Medicine, Detroit, MI, United States.
Department of Biochemistry, Microbiology, and Immunology, Wayne State University School of Medicine, Detroit, MI, United States.
Front Cell Infect Microbiol. 2021 Nov 17;11:780648. doi: 10.3389/fcimb.2021.780648. eCollection 2021.
Coagulase-negative staphylococci (CoNS), including , 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 and models to study the pathobiology of endophthalmitis in mice. We found that is rapidly cleared from mouse eyes, and a relatively higher dose (i.e., 10 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. , 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 endophthalmitis, while tissue damage and visual function loss continue. Thus, our study provides new insights into the pathogenesis of CoNS endophthalmitis.
凝固酶阴性葡萄球菌（CoNS），包括 ，是导致~70%的术后眼内炎的原因，这是一种潜在致盲的眼部感染。然而，CoNS 眼内炎的发病机制仅限于流行病学和临床病例研究，实验研究较少。在这里，我们报告了 和 两种模型，以研究小鼠眼内炎的发病机制。我们发现，在小鼠眼中迅速清除，并且需要相对较高的剂量（即 10 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，随后在 72 小时内逐渐下降。同时也观察到炎症介质和 Toll 样受体（TLR）表达水平的相似时间依赖性下降。相比之下，中性粒细胞浸润持续增加至 72 小时，与视网膜组织损伤和视力丧失显著相关。 ，在小鼠 BMDMs、人 RPE 和视网膜 Muller 胶质细胞中诱导了各种炎症信号通路（即 NF-kB、ERK 和 P38）的激活以及细胞因子和趋化因子的产生。总之，我们表明，在 眼内炎中细菌负荷减少，而组织损伤和视力丧失持续存在。因此，我们的研究为 CoNS 眼内炎的发病机制提供了新的见解。
