title: A Novel CD4+T Cell-Dependent Murine Model of Pneumocystis-driven Asthma-like Pathology.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: 1 Richard King Mellon Foundation Institute for Pediatric Research and.|2 Department of Immunology.
authors.forename: Taylor
authors.initials: T
authors.lastname: Eddens
authors.affiliation: 1 Richard King Mellon Foundation Institute for Pediatric Research and.|3 Division of Pediatric Infectious Diseases, Department of Pediatrics, and.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Campfield
authors.affiliation: 1 Richard King Mellon Foundation Institute for Pediatric Research and.
authors.forename: Katelin
authors.initials: K
authors.lastname: Serody
authors.affiliation: 4 Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Manni
authors.affiliation: 1 Richard King Mellon Foundation Institute for Pediatric Research and.
authors.forename: William
authors.initials: W
authors.lastname: Horne
authors.affiliation: 1 Richard King Mellon Foundation Institute for Pediatric Research and.|2 Department of Immunology.
authors.forename: Waleed
authors.initials: W
authors.lastname: Elsegeiny
authors.affiliation: 4 Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: McHugh
authors.affiliation: 5 Department of Pulmonary Diseases, Critical Care, and Environmental Medicine, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Derek
authors.initials: D
authors.lastname: Pociask
authors.affiliation: 1 Richard King Mellon Foundation Institute for Pediatric Research and.
authors.forename: Kong
authors.initials: K
authors.lastname: Chen
authors.affiliation: 1 Richard King Mellon Foundation Institute for Pediatric Research and.
authors.forename: Mingquan
authors.initials: M
authors.lastname: Zheng
authors.affiliation: 4 Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.
authors.forename: John F
authors.initials: JF
authors.lastname: Alcorn
authors.affiliation: 6 Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and.
authors.forename: Sally
authors.initials: S
authors.lastname: Wenzel
authors.affiliation: 1 Richard King Mellon Foundation Institute for Pediatric Research and.
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
keywords: Pneumocystis; T cells; allergic inflammation; asthma