MyD88 regulation of Fusarium keratitis is dependent on TLR4 and IL-1R1 but not TLR2.
MyD88 regulation of Fusarium keratitis is dependent on TLR4 and IL-1R1 but not TLR2.
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DOI：
10.4049/jimmunol.181.1.593
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发表时间：
2008-07-01
期刊：
影响因子：
--
通讯作者：
Pearlman E
中科院分区：
文献类型：
--
作者：
Tarabishy AB;Aldabagh B;Sun Y;Imamura Y;Mukherjee PK;Lass JH;Ghannoum MA;Pearlman E
真菌病原体茄病镰刀菌（Fusarium solani）和尖孢镰刀菌（Fusarium oxysporum）在美国和世界范围内引起严重的角膜疾病，并且是最近爆发的接触镜相关角膜炎的病原体。为了表征镰刀菌角膜炎的先天免疫，我们开发了一种将分生孢子注射到角膜基质中的小鼠模型。免疫活性的C57 BL/6小鼠迅速发生严重的角膜混浊，伴有中性粒细胞浸润和镰刀菌菌丝清除。相比之下，MyD 88 −/−小鼠的中性粒细胞浸润延迟，导致角膜基质和前房中镰刀菌菌丝的不受控制的生长，最终导致角膜穿孔。TLR 2 −/−、TLR 4 −/−和TLR 2/4−/−小鼠的角膜混浊评分与C57 BL/6小鼠相似;然而，TLR 4 −/−和TLR 2/4−/−小鼠的抗真菌反应受损。感染IL-1 R1 −/−小鼠的表型与MyD 88 −/−小鼠相似，真菌生长不受控制，导致角膜穿孔。与C57 BL/6小鼠相比，IL-1 R1 −/−小鼠在角膜基质中产生的CXCL 1/KC也显著减少，这与中性粒细胞向角膜基质的延迟募集一致。总之，这些发现表明IL-1 R1和MyD 88调节CXC趋化因子的产生和中性粒细胞向角膜的募集，并且TLR 4在控制这些病原性真菌的生长和复制方面具有重要作用。
The fungal pathogens Fusarium solani and Fusarium oxysporum cause severe corneal disease in the United States and worldwide and were the causative organisms in a recent outbreak of contact lens-associated keratitis. To characterize innate immunity in Fusarium keratitis, we developed a murine model in which conidia are injected into the corneal stroma. Immunocompetent C57BL/6 mice rapidly developed severe corneal opacification associated with neutrophil infiltration and clearance of Fusarium hyphae. In contrast, neutrophil infiltration was delayed in MyD88−/− mice, resulting in uncontrolled growth of Fusarium hyphae in the corneal stroma and anterior chamber, and eventually resulting in corneal perforation. Corneal opacification scores in TLR2−/−, TLR4−/−, and TLR2/4−/− mice were similar to those of C57BL/6 mice; however, TLR4−/− and TLR2/4−/− mice had impaired antifungal responses. The phenotype of infected IL-1R1−/− mice was similar to that of MyD88−/− mice, with uncontrolled fungal growth resulting in corneal perforation. IL-1R1−/− mice also produced significantly less CXCL1/KC in the corneal stroma compared with C57BL/6 mice consistent with delayed neutrophil recruitment to the corneal stroma. Together, these findings indicate that IL-1R1 and MyD88 regulate CXC chemokine production and neutrophil recruitment to the cornea, and that TLR4 has an important role in controlling growth and replication of these pathogenic fungi.
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3
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