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沙眼衣原体人生物变种眼部感染的小鼠模型

Murine model of ocular infection by a human biovar of Chlamydia trachomatis.

作者信息

Whittum-Hudson J A, O'Brien T P, Prendergast R A

机构信息

Wilmer Ophthalmological Institute, Johns Hopkins University, Baltimore, Maryland, USA.

出版信息

Invest Ophthalmol Vis Sci. 1995 Sep;36(10):1976-87.

PMID:7657540
Abstract

PURPOSE

A human biovar of Chlamydia trachomatis was used to develop a murine model of ocular chlamydial infection. The inbred mouse model will allow detailed immunologic studies during ocular infection, and use of a human biovar for infection may aid in identification of appropriate vaccine strategies against chlamydial infections.

METHODS

BALB/c, C3H/HeN, and C57B1/6J mice (n = 5 to 10 mice/group) were topically infected in the conjunctiva with C serovar of C. trachomatis. The effects were tested of single and repeated infection with 5000 inclusion-forming units (IFU) in 5 microliters and different inoculum doses. Conjunctival surfaces of both eyes were swabbed for microbiologic signs (isolation culture or direct fluorescent antibody staining) of infection over 4 to 6 weeks. Conjunctivae were removed for histopathologic study, and lymphocytes from draining cervical lymph nodes and spleens were tested for chlamydia-specific proliferative responses. Serum was obtained from all mice and tested for anti-chlamydial antibodies.

RESULTS

BALB/c and C3H/HeN mice developed dose-dependent microbiologic, histopathologic, and immunologic evidence of ocular infection. Eyes of mice were culture-positive from day 7 through at least day 21, with the peak of infection at days 10 to 14 after infection. Histopathologically, the development of conjunctival subepithelial mononuclear infiltration, exudate, and loss of goblet cells occurred within 1 week. Dose-dependent lymphoproliferative responses to whole chlamydial elementary bodies were observed; anti-chlamydial antibody was detected by immunoblotting only in infected mice.

CONCLUSIONS

Several strains of inbred mice are susceptible to human chlamydial biovars and may provide a useful alternative disease model in which to study the immunopathogenesis of ocular chlamydial infection and test of vaccine candidates derived from clinically relevant human biovars.

摘要

目的

利用沙眼衣原体的一个人类生物变种建立眼部衣原体感染的小鼠模型。近交系小鼠模型将有助于在眼部感染期间进行详细的免疫学研究,使用人类生物变种进行感染可能有助于确定针对衣原体感染的合适疫苗策略。

方法

将BALB/c、C3H/HeN和C57B1/6J小鼠(每组n = 5至10只小鼠)的结膜局部感染沙眼衣原体的C血清型。测试了5微升中5000个包涵体形成单位(IFU)的单次和重复感染以及不同接种剂量的效果。在4至6周内擦拭双眼结膜表面,以寻找感染的微生物学迹象(分离培养或直接荧光抗体染色)。取出结膜进行组织病理学研究,并检测引流颈淋巴结和脾脏中的淋巴细胞对衣原体的特异性增殖反应。从所有小鼠获取血清并检测抗衣原体抗体。

结果

BALB/c和C3H/HeN小鼠出现了眼部感染的剂量依赖性微生物学、组织病理学和免疫学证据。小鼠的眼睛从第7天至至少第21天培养呈阳性,感染高峰在感染后第10至14天。组织病理学上,结膜上皮下单核细胞浸润、渗出物和杯状细胞丢失在1周内出现。观察到对整个衣原体原体的剂量依赖性淋巴细胞增殖反应;仅在感染小鼠中通过免疫印迹检测到抗衣原体抗体。

结论

几种近交系小鼠品系对人类衣原体生物变种易感,可能为研究眼部衣原体感染的免疫发病机制和测试源自临床相关人类生物变种的候选疫苗提供有用的替代疾病模型。

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