Chronic Infection by Mucoid Pseudomonas aeruginosa Associated with Dysregulation in T-Cell Immunity to Outer Membrane Porin F. Academic Article uri icon

Overview

MeSH

  • Adult
  • Aged
  • Animals
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Mice
  • Middle Aged
  • Sputum
  • Young Adult

MeSH Major

  • Lung
  • Porins
  • Pseudomonas Infections
  • Pseudomonas aeruginosa
  • T-Lymphocytes

abstract

  • 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. To characterize T-cell immunity to the PA antigen outer membrane porin F (OprF) by analyzing immunodominant epitopes in relation to infection status. 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. 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. 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.

publication date

  • June 1, 2015

has subject area

  • Adult
  • Aged
  • Animals
  • Female
  • Humans
  • Longitudinal Studies
  • Lung
  • Male
  • Mice
  • Middle Aged
  • Porins
  • Pseudomonas Infections
  • Pseudomonas aeruginosa
  • Sputum
  • T-Lymphocytes
  • Young Adult

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4476516

Digital Object Identifier (DOI)

  • 10.1164/rccm.201411-1995OC

PubMed ID

  • 25789411

Additional Document Info

start page

  • 1250

end page

  • 1264

volume

  • 191

number

  • 11