2012年10月26日 讯 /生物谷BIOON/ --隐形眼镜,特别是长戴型隐形眼镜,使得眼镜佩戴者容易眼镜被铜绿假单胞菌(Pseudomonas aeruginosa)感染。这些感染能够导致严重性损伤,包括失明。在模式小鼠中,利用针对炎性免疫化合物白细胞介素17(interleukin-17, IL-17)的抗体治疗眼睛降低眼睛损伤和细菌数量。相关研究结果发表在Infection and Immunity期刊上。
假单胞菌对眼睛的感染经常是快速的,而且当这种细菌对抗生素产生耐药性时,感染后的结果更加严重。
在假单胞菌感染之后,被称作嗜中性粒细胞的免疫细胞时导致眼睛损伤的主要原因。IL-17参与吸引嗜中性粒细胞到被感染的组织。这些免疫细胞时免疫攻击的先锋:在1个小时内到达感染位点,捕获和吞噬病原菌。在杀病原菌的过程中,它们也释放有害物质,特别是弹性蛋白酶(elastase)和超氧化物,其中弹性蛋白酶能够损害组织,而超氧化物能够被转化为次氯酸。因此,随后发生的眼睛损伤并不令人感到惊奇。
不过,论文通讯作者、美国布莱根妇女医院研究员Gregory P. Priebe说,阻断这些病原菌杀死细胞的策略会冒着降低免疫系统杀菌功能的风险。Priebe.说,“令人吃惊的是,与观察到的情形相反的是:利用抗体阻断IL-17导致眼睛拥有更少的嗜中性粒细胞和更少的细菌。”因此,他说,这项研究可能导致人们开发出新的有效疗法。(生物谷:Bioon.com)
doi: 10.1128/IAI.00249-12
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Topical neutralization of interleukin-17 during experimental Pseudomonas aeruginosa corneal infection promotes bacterial clearance and reduces pathology
T.S. Zaidi, T. Zaidi, G.B. Pier, and G.P. Priebe
The proinflammatory cytokine interleukin-17 (IL-17) is involved in neutrophilic tissue infiltration, contributing to both microbial clearance as well as inflammation-associated tissue damage. Its role during bacterial corneal infections is unknown. We hypothesized that IL-17 responses would be detrimental in this setting and tested the impact of IL-17 receptor deficiency or antibody-mediated neutralization of IL-17 in a murine model of Pseudomonas aeruginosa ulcerative keratitis after scratch injury. We found that, compared with infected corneas from wild-type mice, those from IL-17 receptor (IL-17R)-deficient mice had significantly lower corneal pathology scores, neutrophil influx, and intracellular bacterial levels. Infected IL-17R-deficient corneas had low intercellular adhesion molecule 1 (ICAM-1) expression, and ICAM-1-deficient mice were similarly resistant to infection. Topical treatment with polyclonal antibodies to IL-17 resulted in significant reductions in corneal pathology and also lowered bacterial counts after infection with six different laboratory or clinical P. aeruginosa strains, including both invasive and cytotoxic strains. Thus, neutralization of IL-17 during P. aeruginosa corneal infection reduces neutrophil influx and pathology without compromising bacterial clearance and offers a promising new avenue for therapy of these potentially sight-threatening infections.