Chronic Infection by Mucoid Pseudomonas aeruginosa Associated with Dysregulation in T-Cell Immunity to Outer Membrane Porin F

American Journal of Respiratory and Critical Care Medicine
Kathryn J QuigleyRosemary J Boyton

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 redu...Continue Reading

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Citations

Mar 17, 2016·Annual Review of Pathology·Rosemary J Boyton, Daniel M Altmann
Jun 21, 2016·Respirology : Official Journal of the Asian Pacific Society of Respirology·Yong-Hua GaoGuo-Jun Zhang
Mar 10, 2016·PLoS Computational Biology·Lies BoelenBecca Asquith
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Jun 8, 2018·Breathe·Celine VidaillacSanjay H Chotirmall
Mar 1, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Catherine J ReynoldsRosemary J Boyton
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Sep 5, 2019·The New England Journal of Medicine·Richard C Boucher
Jul 15, 2021·Seminars in Respiratory and Critical Care Medicine·Holly R Keir, James D Chalmers

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