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鼠 β-防御素 3 和 4 及抗菌肽 cathelin 相关肽在茄病镰刀菌角膜炎中的保护作用。

Protective role of murine β-defensins 3 and 4 and cathelin-related antimicrobial peptide in Fusarium solani keratitis.

机构信息

University of Houston, College of Optometry, Houston, Texas, USA.

出版信息

Infect Immun. 2013 Aug;81(8):2669-77. doi: 10.1128/IAI.00179-13. Epub 2013 May 13.

Abstract

Antimicrobial peptides (AMPs), such as β-defensins and cathelicidins, are essential components of innate and adaptive immunity owing to their extensive multifunctional activities. However, their role in fungal infection in vivo remains elusive. In this study, we investigated the protective effect of murine β-defensin 3 (mBD3), mBD4, and the cathelicidin cathelin-related antimicrobial peptide (CRAMP) in a murine model of Fusarium solani keratitis. C57BL/6 mice showed significant corneal disease 1 and 3 days after infection, which was accompanied by enhanced expression of β-defensins and CRAMP. Disease severity was significantly improved 7 days after infection, at which time AMP expression was returning to baseline. Mice deficient in mBD3 (genetic knockout), mBD4 (short interfering RNA knockdown), or CRAMP (genetic knockout) exhibited enhanced disease severity and progression, increased neutrophil recruitment, and delayed pathogen elimination compared to controls. Taken together, these data suggest a vital role for AMPs in defense against F. solani keratitis, a potentially blinding corneal disease.

摘要

抗菌肽(AMPs),如β-防御素和cathelicidins,由于其广泛的多功能活性,是先天和适应性免疫的重要组成部分。然而,它们在体内真菌感染中的作用仍不清楚。在这项研究中,我们研究了鼠β-防御素 3(mBD3)、mBD4 和 cathelicidin 相关抗菌肽(CRAMP)在 Fusarium solani 角膜炎小鼠模型中的保护作用。C57BL/6 小鼠在感染后 1 天和 3 天表现出明显的角膜疾病,同时β-防御素和 CRAMP 的表达增强。感染后 7 天,疾病严重程度显著改善,此时 AMP 表达恢复基线。与对照组相比,mBD3(基因敲除)、mBD4(短发夹 RNA 敲低)或 CRAMP(基因敲除)缺陷小鼠表现出更严重的疾病和进展、增加的中性粒细胞募集和延迟的病原体清除。综上所述,这些数据表明 AMPs 在防御 Fusarium solani 角膜炎(一种潜在致盲性角膜疾病)中起着至关重要的作用。

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