title: Chronic Infection by Mucoid Pseudomonas aeruginosa Associated with Dysregulation in T-Cell Immunity to Outer Membrane Porin F.
abstract: BACKGROUND
  Pseudomonas aeruginosa (PA) is an environmental pathogen that commonly infects individuals with cystic fibrosis (CF) and non-CF bronchiectasis, impacting morbidity and mortality. To understand the pathobiology of interactions between the bacterium and host adaptive immunity and to inform rational vaccine design, it is important to understand the adaptive immune correlates of disease.
  
  
  OBJECTIVE
  To characterize T-cell immunity to the PA antigen outer membrane porin F (OprF) by analyzing immunodominant epitopes in relation to infection status.
  
  
  METHODS
  Patients with non-CF bronchiectasis were stratified by frequency of PA isolation. T-cell IFN-γ immunity to OprF and its immunodominant epitopes was characterized. Patterns of human leukocyte antigen (HLA) restriction of immunodominant epitopes were defined using HLA class II transgenic mice. Immunity was characterized with respect to cytokine and chemokine secretion, antibody response, and T-cell activation transcripts.
  
  
  RESULTS
  Patients were stratified according to whether PA was never, sometimes (<50%), or frequently (≥50%) isolated from sputum. Patients with frequent PA sputum-positive isolates were more likely to be infected by mucoid PA, and they showed a narrow T-cell epitope response and a relative reduction in Th1 polarizing transcription factors but enhanced immunity with respect to antibody production, innate cytokines, and chemokines.
  
  
  CONCLUSIONS
  We have defined the immunodominant, HLA-restricted T-cell epitopes of OprF. Our observation that chronic infection is associated with a response of narrowed specificity, despite strong innate and antibody immunity, may help to explain susceptibility in these individuals and pave the way for better vaccine design to achieve protective immunity.
authors: 1 Lung Immunology Group, Infectious Diseases and Immunity, Department of Medicine, Medical Research Council and Asthma United Kingdom Centre in Allergic Mechanisms of Asthma, Centre for Respiratory Infection, Hammersmith Hospital, Imperial College, London, United Kingdom.
authors: Kathryn J
authors: KJ
authors: Quigley
authors: Catherine J
authors: CJ
authors: Reynolds
authors: Amelie
authors: A
authors: Goudet
authors: Eleanor J
authors: EJ
authors: Raynsford
authors: Ruhena
authors: R
authors: Sergeant
authors: Andrew
authors: A
authors: Quigley
authors: Stefan
authors: S
authors: Worgall
authors: Diana
authors: D
authors: Bilton
authors: Robert
authors: R
authors: Wilson
authors: Michael R
authors: MR
authors: Loebinger
authors: Bernard
authors: B
authors: Maillere
authors: Daniel M
authors: DM
authors: Altmann
authors: Rosemary J
authors: RJ
authors: Boyton
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008168:Lung / Q000276:immunology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D018272:Porins / Q000276:immunology*; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D013183:Sputum / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
chemical_list: D018272:Porins
keywords: Pseudomonas; T lymphocyte; adaptive immunity; bronchiectasis; epitopes