Expression of Innate and Adaptive Immune Mediators in Human Corneal Tissue Infected With Aspergillus or Fusarium

Expression of Innate and Adaptive Immune Mediators in Human Corneal Tissue Infected With Aspergillus or Fusarium
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DOI:
10.1093/infdis/jir426
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发表时间:
2011-09-15
影响因子:
6.4
通讯作者:
Lalitha, Prajna
Lalitha, Prajna
中科院分区:
医学2区
文献类型:
--
作者:
Karthikeyan, Rajapandian Sivaganesa;Leal, Sixto M., Jr.;Lalitha, Prajna

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背景资料。曲霉属和镰刀菌属的丝状真菌是美国和发展中国家角膜溃疡的主要原因,并导致严重的视力损伤和失明。在印度南部,110例角膜溃疡患者在感染茄病镰刀菌或黄曲霉后1周内提取RNA,用定量聚合酶链式反应检测基因表达。晚期疾病的移植后角膜(.感染后2周)同时进行检查。与未感染的供体角膜相比,Dectin-1、Toll样受体2(TLR2)、TLR4、TLR9和Nod-like Receptor Protein(NLRP)3信使RNA的表达增加了1000倍,而Dectin-2在未感染的角膜中呈结构性表达。此外,白介素1β(IL-1β)的表达增加了1000倍,而IL-1α的表达没有增加。IL-8、IL-17和肿瘤坏死因子α的表达也升高。在感染后的角膜中检测到CD3(+)和CD4(+)T细胞。IL-17和干扰素c表达升高,而IL-4表达无明显变化。曲霉菌和镰刀菌感染的角膜在任一时间点的宿主反应均无显著差异。对这些丝状真菌有一种常见的先天和获得性免疫反应,包括T辅助细胞1和T辅助17细胞的产生。
Background. Filamentous fungi of the genera Aspergillus and Fusarium are major causes of corneal ulcers in the United States and in the developing world and result in significant visual impairment and blindness.Methods. RNA was extracted from 110 patients with corneal ulcers in southern India within 1 week of infection with either Fusarium solani or Aspergillus flavus, and gene expression was determined by quantitative polymerase chain reaction. Posttransplant corneas from later stage disease (. 2 weeks after infection) were also examined.Results. Expression of Dectin-1, Toll-like receptor 2 (TLR2), TLR4, TLR9, and NOD-like receptor protein (NLRP) 3 messenger RNA was elevated >1000-fold compared with uninfected donor corneas, whereas Dectin-2 was constitutively expressed in uninfected corneas. Furthermore, interleukin 1 beta (IL-1 beta) expression was elevated >1000-fold, whereas IL-1 alpha expression was not increased. Expression of IL-8, IL-17, and tumor necrosis factor alpha was also elevated. CD3(+) and CD4(+) T cells were detected in infected posttransplant corneas. Expression of IL-17 and interferon c was elevated but not that of IL-4. There were no significant differences in the host response between Aspergillus-and Fusarium-infected corneas at any time point.Conclusions. There is a common innate and adaptive immune response to these filamentous fungi, which includes the generation of T-helper 1 and T-helper 17 cells.