2012年10月26日 訊 /生物谷BIOON/ --隱形眼鏡，特別是長戴型隱形眼鏡,，使得眼鏡佩戴者容易眼鏡被銅綠假單胞菌(Pseudomonas aeruginosa)感染,。這些感染能夠?qū)е聡乐匦該p傷，包括失明,。在模式小鼠中,，利用針對炎性免疫化合物白細胞介素17(interleukin-17, IL-17)的抗體治療眼睛降低眼睛損傷和細菌數(shù)量。相關(guān)研究結(jié)果發(fā)表在Infection and Immunity期刊上,。
假單胞菌對眼睛的感染經(jīng)常是快速的,，而且當這種細菌對抗生素產(chǎn)生耐藥性時，感染后的結(jié)果更加嚴重。
在假單胞菌感染之后,，被稱作嗜中性粒細胞的免疫細胞時導(dǎo)致眼睛損傷的主要原因,。IL-17參與吸引嗜中性粒細胞到被感染的組織。這些免疫細胞時免疫攻擊的先鋒：在1個小時內(nèi)到達感染位點,，捕獲和吞噬病原菌,。在殺病原菌的過程中，它們也釋放有害物質(zhì),，特別是彈性蛋白酶(elastase)和超氧化物,，其中彈性蛋白酶能夠損害組織，而超氧化物能夠被轉(zhuǎn)化為次氯酸,。因此,，隨后發(fā)生的眼睛損傷并不令人感到驚奇。
不過,，論文通訊作者,、美國布萊根婦女醫(yī)院研究員Gregory P. Priebe說，阻斷這些病原菌殺死細胞的策略會冒著降低免疫系統(tǒng)殺菌功能的風險,。Priebe.說,，“令人吃驚的是，與觀察到的情形相反的是：利用抗體阻斷IL-17導(dǎo)致眼睛擁有更少的嗜中性粒細胞和更少的細菌,。”因此,，他說，這項研究可能導(dǎo)致人們開發(fā)出新的有效療法,。(生物谷：Bioon.com)
doi: 10.1128/IAI.00249-12
PMC:
PMID:
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.
