Fas ligand but not complement is critical for control of experimental Staphylococcus aureus endophthalmitis
Fas ligand but not complement is critical for control of experimental Staphylococcus aureus endophthalmitis
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DOI：
10.1167/iovs.04-1139
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发表时间：
2005-07-01
影响因子：
4.4
通讯作者：
Gilmore, MS
中科院分区：
文献类型：
--
作者：
Engelbert, M;Gilmore, MS
目的。目的探讨补体和Fas配体（FasL）在宿主抗金黄色葡萄球菌眼内炎中的作用。用500和5000 CFU金黄色葡萄球菌感染C3（-/-）、FasL缺陷金和C57/BL6（野生型[WT]）小鼠，通过眼内细菌计数、ERG检测视网膜功能、组织病理学和流式细胞术检测形态学损伤和炎症。在注射500 CFU的WT眼中，金黄色葡萄球菌在24小时内生长到1 × 10(7) CFU/mL，但在96小时内被清除。在注射5000 CFU的WT眼中，72小时后金黄色葡萄球菌生长到2 × 10(9) CFU/mL，导致角膜穿孔。注射500 CFU的C3（-/-）眼的水平暂时高于WT组（P < 0.001），但最终的过程相似。感染500 CFU的金眼与感染5000 CFU的WT眼细菌计数相似。在WT和C3（-/-）眼注射500 CFU后，视网膜功能仅短暂下降，72小时后恢复到66%。注射5000 CFU的WT眼和感染500 CFU的金眼在24小时内视网膜功能完全丧失。24小时时，注射500 CFU的WT和C3（-/-）眼均有相似数量的粒细胞浸润，但金眼的招募明显受损（P < 0.005）。WT和C3（-/-）眼的细胞计数此后下降，无明显的视网膜疾病。在注射5000 CFU的眼和感染500 CFU的金眼中，炎症细胞在48小时内完全填满眼腔。视网膜和葡萄膜组织被破坏。在这种小鼠眼内炎模型中，好与坏结果的临界点介于500和5000 CFU之间。这一点在缺乏补体激活的动物中是相同的，这表明补体在眼部防御眼内细菌方面没有发挥重要作用。相反，FasL被发现对清除至关重要，因为FasL信号缺乏的动物无法控制500 CFU的感染。
PURPOSE. To determine the role of complement and Fas Ligand (FasL) in the host defense against Staphylococcus aureus endophthalmitis.METHODS. C3(-/-), FasL defective gld, and C57/BL6 (wild-type [WT]) mice were infected intravitreally with 500 and 5000 CFU S. aureus, and the course of infection was followed by determining the intraocular bacteria counts, retinal function by ERG, and morphologic damage and inflammation by histopathology and flow cytometry.RESULTS. In WT eyes injected with 500 CFU, S. aureus grew to 1 x 10(7) CFU/mL by 24 hours, but was cleared by 96 hours. In the WT eyes injected with 5000 CFU, S. aureus grew to 2 x 10(9) CFU/mL by 72 hours, resulting in corneal perforation. C3(-/-) eyes injected with 500 CFU reached transiently higher levels than their WT counterparts (P < 0.001), but eventually followed a similar course. Bacterial counts in gld eyes infected with 500 CFU were similar to those in WT eyes infected with 5000 CFU. In WT and C3(-/-) eyes injected with 500 CFU, retinal function decreased only transiently and recovered to 66% in 72 hours. In WT eyes injected with 5000 CFU and gld eyes infected with 500 CFU, retinal function was completely lost by 24 hours. By 24 hours, WT and C3(-/-) eyes injected with 500 CFU were infiltrated with a similar number of granulocytes, but recruitment was significantly impaired in gld eyes (P < 0.005). Cell counts in WT and C3(-/-) eyes decreased thereafter without overt retinal disease. In eyes injected with 5000 CFU and gld eyes infected with 500 CFU, inflammatory cells completely filled the intraocular space by 48 hours. Retinal and uveal tissue was destroyed by that time.CONCLUSIONS. The tipping point for a good versus a bad outcome in this murine model of endophthalmitis lies between 500 and 5000 CFU S. aureus. This point is identical in animals deficient in complement activation, suggesting that complement does not play a significant role in the ocular defense against intraocular bacteria. In contrast, FasL was found to be critical for clearance, since animals deficient in FasL signaling were unable to control infection with 500 CFU.