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

Abstract：

RATIONALE: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. OBJECTIVES:We sought to explore the role of Pneumocystis in generating asthma-like lung pathology, given the natural eosinophilic response to infection. 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.

journal_name

Am J Respir Crit Care Med

journal_title

American journal of respiratory and critical care medicine

authors

Eddens T,Campfield BT,Serody K,Manni ML,Horne W,Elsegeiny W,McHugh KJ,Pociask D,Chen K,Zheng M,Alcorn JF,Wenzel S,Kolls JK

doi

10.1164/rccm.201511-2205OC

subject

Has Abstract

pub_date

2016-10-01 00:00:00

pages

807-820

issue

eissn

1073-449X

issn

1535-4970

journal_volume

194

pub_type

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