Loading…

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

Infection with Pneumocystis, an opportunistic fungal pathogen, can result in fulminant pneumonia in the clinical setting of patients with immunosuppression. In murine models, Pneumocystis has previously been shown to induce a CD4 T cell-dependent eosinophilic response in the lung capable of providin...

Full description

Saved in:
Bibliographic Details
Published in:American journal of respiratory and critical care medicine 2016-10, Vol.194 (7), p.807-820
Main Authors: Eddens, Taylor, Campfield, Brian T, Serody, Katelin, Manni, Michelle L, Horne, William, Elsegeiny, Waleed, McHugh, Kevin J, Pociask, Derek, Chen, Kong, Zheng, Mingquan, Alcorn, John F, Wenzel, Sally, Kolls, Jay K
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Infection with Pneumocystis, an opportunistic fungal pathogen, can result in fulminant pneumonia in the clinical setting of patients with immunosuppression. In murine models, Pneumocystis has previously been shown to induce a CD4 T cell-dependent eosinophilic response in the lung capable of providing protection. We sought to explore the role of Pneumocystis in generating asthma-like lung pathology, given the natural eosinophilic response to infection. 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. 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. The present study demonstrates for the first time, to our knowledge, that Pneumocystis is an airway allergen capable of inducing asthma-like lung pathology.
ISSN:1073-449X
1535-4970
DOI:10.1164/rccm.201511-2205OC