A Novel CD4+ T Cell-Dependent Murine Model of Pneumocystis-driven Asthma-like Pathology

一种新型 CD4+ T 细胞依赖性小鼠肺孢子虫驱动的哮喘样病理模型

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作者:Taylor Eddens, Brian T Campfield, Katelin Serody, Michelle L Manni, William Horne, Waleed Elsegeiny, Kevin J McHugh, Derek Pociask, Kong Chen, Mingquan Zheng, John F Alcorn, Sally Wenzel, Jay K Kolls

Conclusions

The present study demonstrates for the first time, to our knowledge, that Pneumocystis is an airway allergen capable of inducing asthma-like lung pathology.

Methods

Pneumocystis infection or antigen treatment was used to induce asthma-like pathology in wild-type mice. The roles of CD4+ T cells and eosinophils were examined using antibody depletion and knockout mice, respectively. The presence of anti-Pneumocystis antibodies in human serum samples was detected by ELISA and Western blotting. Measurements and main

Results

Pneumocystis infection generates a strong type II response in the lung that requires CD4+ T cells. Pneumocystis infection was capable of priming a Th2 response similar to that of a commonly studied airway allergen, the house dust mite. Pneumocystis antigen treatment was also capable of inducing allergic inflammation in the lung, resulting in anti-Pneumocystis IgE production, goblet cell hyperplasia, and increased airway resistance. In the human population, patients with severe asthma had increased levels of anti-Pneumocystis IgG and IgE compared with healthy control subjects. Patients with severe asthma with elevated anti-Pneumocystis IgG levels had worsened symptom scores and lung parameters such as decreased forced expiratory volume and increased residual volume compared with patients with severe asthma who had low anti-Pneumocystis IgG. Conclusions: The present study demonstrates for the first time, to our knowledge, that Pneumocystis is an airway allergen capable of inducing asthma-like lung pathology.

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