T和B细胞缺陷对真菌性角膜炎发病过程的影响(英文)

Combined deficiency of T and B cells impact on the initiation of Aspergillus or Candida keratitis in murine models

目的:探讨特异性免疫应答是否参与真菌性角膜炎(fungalkeratitis,FK)发病早期的病理过程。方法:通过角膜基质内注射1×105白色念珠菌孢子或烟曲霉菌孢子的方法在相同免疫遗传背景的Balb/c小鼠和重症联合免疫缺陷小鼠(severecombinedT/B-nullimmuno-deficiency,SCID)诱导FK。用裂隙灯监测疾病临床变化特征并依据角膜病灶面积和病变深度以及角膜表面规则性进行临床评分。在病变显著的时间点,摘除小鼠眼球用HE和PAS染色观察小鼠角膜组织的病理变化特征。用菌落形成实验检测角膜组织中活菌数量的变化,用ELISA检测小鼠血浆和角膜组织匀浆液中细胞因子IL17、IFNγ和IL10的动态变化。结果:Balb/c小鼠和SCID小鼠都可诱导出典型的FK。在白念菌性角膜炎或烟曲霉菌性角膜炎中,无论是大体临床表现和疾病分数,抑或组织病理变化和真菌负荷分析,在两种小鼠之间均无显著性差异;两种小鼠间在血浆或角膜组织中IL17及IFNγ的水平等方面也没有显着差异。但诱导两种FK的SCID小鼠中,无论角膜匀浆液抑或外周血浆,在任何时间点均检测不到IL10的表达,而同样发生角膜炎的Balb/c小鼠则在FK发病早期检测到IL10的表达。结论:在免疫遗传背景相同的条件下,小鼠中获得性免疫组分的存在与否并不影响FK的发病过程,提示小鼠中初次FK的发病与固有性免疫组分相关。

AIM： To explore whether adaptive immunity is involved in initiation of fungal keratitis （FK）. METHODS： Balb/c mice and severe combined T/B-null immunodeficiency （SCID） mice on same background were subjected to keratitis induction via intrastromal injection of 1 × 105 Candida albican or Aspergillus fumigatus spores. The disease was monitored using slit-lamp and scored according to area and density of opacity and surface irregularity of the affected corneas. At desired time points, murine eyes were enucleated for histological examination by hematoxylin- eosin and Periodic acid Schiff staining. The number of live-fungi in corneal tissue was detected with colony forming assay, and the levels of IL17, IFNγ and IL10 in plasma and corneal tissue homogenate were evaluated by ELISA. RESULTS： Both Balb/c mice and SCID mice developed typical keratitis when subjected to FK induction. Gross clinical presentation and disease scoring, as well as histology and pathogen load assay showed no significant difference between Balb/c mice and SCID mice with either pathogen. With the cytokine levels in either plasma or cornea, neither IL17 nor IFNy showed significant difference between these two mouse strains, but IL10 was undetectable in any SCID mice though it could be detected in Balb/c mice, especially at early time points after FK induction. CONCLUSION： The presence or absence of adaptive immunity compartment, at least in the studied Balb/c and SCID mice pairing, does not alter the course of primary FK, supporting the hypothesis that innate immunity component is more relevant with the pathogenesis of FK.