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实验性小鼠球孢子菌病中活性氧中间体的作用。

The role of reactive oxygen intermediates in experimental coccidioidomycois in mice.

机构信息

Veterans Affairs San Diego Healthcare System (111F) 3350 La Jolla Village Dr, San Diego, CA 92161, USA.

出版信息

BMC Microbiol. 2011 Apr 11;11:71. doi: 10.1186/1471-2180-11-71.

DOI:10.1186/1471-2180-11-71
PMID:21481258
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3088889/
Abstract

BACKGROUND

Coccidioidomycosis is usually a self-limited infection in immunocompentent people. In immunocompentent human beings second infections due to Coccidioides are very rare, indicating that recovery from infection results in protective immunity. In experimental animals, immunization with several different proteins or attenuated mutants protects against a virulent challenge. To explore what mechanisms are responsible for protective immunity, we investigated the course of Coccidioides infection in the gp91phox knock out mouse that has a defect in the oxidative burst that results in chronic granulomatous disease.

RESULTS

We found that the gp91phox knock out mice were somewhat more resistant to intraperitoneal infection and equally as resistant to low dose intranasal infection, but slightly more susceptible to high dose intranasal infection compared to control mice. The gp91phox knock out mice made a more robust inflammatory response to infection than controls, as measured by histology and production of inflammatory cytokines. The gp91phox knock out mice were as protected by immunization with the recombinant Coccidioides protein Ag2/PRA as the controls were against either intraperitoneal or intranasal infection. Coccidioides immitis arthroconidia and spherules were significantly more resistant to H2O2 treatment in vitro than Aspergillus fumigatus spores.

CONCLUSION

These data suggest that oxidative burst may not be required for protective immunity to coccidioidomycois.

摘要

背景

球孢子菌病在免疫功能正常的人群中通常是一种自限性感染。在免疫功能正常的人群中,由于球孢子菌引起的二次感染非常罕见,这表明感染的恢复会产生保护性免疫。在实验动物中,用几种不同的蛋白质或减毒突变体免疫可预防强毒攻击。为了探讨什么机制负责保护性免疫,我们研究了 gp91phox 敲除小鼠中的球孢子菌感染过程,该小鼠在氧化爆发中存在缺陷,导致慢性肉芽肿病。

结果

我们发现,gp91phox 敲除小鼠对腹腔感染的抵抗力略高,对低剂量鼻腔感染的抵抗力与对照小鼠相当,但对高剂量鼻腔感染的抵抗力略低。与对照小鼠相比,gp91phox 敲除小鼠对感染的炎症反应更为强烈,这可以通过组织学和炎症细胞因子的产生来衡量。gp91phox 敲除小鼠对重组球孢子菌蛋白 Ag2/PRA 的免疫保护作用与对照小鼠对腹腔或鼻腔感染的保护作用相当。与烟曲霉孢子相比,球孢子菌的分生孢子和球形小体在体外对 H2O2 处理的抵抗力明显更强。

结论

这些数据表明,氧化爆发可能不是针对球孢子菌病的保护性免疫所必需的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d39/3088889/f726f695acb5/1471-2180-11-71-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d39/3088889/319c01b2945f/1471-2180-11-71-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d39/3088889/d6fd8627a9b6/1471-2180-11-71-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d39/3088889/62e2958ad6fc/1471-2180-11-71-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d39/3088889/263777f12359/1471-2180-11-71-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d39/3088889/f726f695acb5/1471-2180-11-71-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d39/3088889/319c01b2945f/1471-2180-11-71-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d39/3088889/d6fd8627a9b6/1471-2180-11-71-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d39/3088889/62e2958ad6fc/1471-2180-11-71-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d39/3088889/263777f12359/1471-2180-11-71-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d39/3088889/f726f695acb5/1471-2180-11-71-5.jpg

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