PMID- 25789411
OWN - NLM
STAT- MEDLINE
DCOM- 20150817
LR  - 20220317
IS  - 1535-4970 (Electronic)
IS  - 1073-449X (Print)
IS  - 1073-449X (Linking)
VI  - 191
IP  - 11
DP  - 2015 Jun 1
TI  - Chronic Infection by Mucoid Pseudomonas aeruginosa Associated with Dysregulation 
      in T-Cell Immunity to Outer Membrane Porin F.
PG  - 1250-64
LID - 10.1164/rccm.201411-1995OC [doi]
AB  - RATIONALE: 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. 
      OBJECTIVES: 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-gamma 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. MEASUREMENTS AND MAIN 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.
FAU - Quigley, Kathryn J
AU  - Quigley KJ
AD  - 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.
FAU - Reynolds, Catherine J
AU  - Reynolds CJ
FAU - Goudet, Amelie
AU  - Goudet A
FAU - Raynsford, Eleanor J
AU  - Raynsford EJ
FAU - Sergeant, Ruhena
AU  - Sergeant R
FAU - Quigley, Andrew
AU  - Quigley A
FAU - Worgall, Stefan
AU  - Worgall S
FAU - Bilton, Diana
AU  - Bilton D
FAU - Wilson, Robert
AU  - Wilson R
FAU - Loebinger, Michael R
AU  - Loebinger MR
FAU - Maillere, Bernard
AU  - Maillere B
FAU - Altmann, Daniel M
AU  - Altmann DM
FAU - Boyton, Rosemary J
AU  - Boyton RJ
LA  - eng
GR  - 272200900046C/PHS HHS/United States
GR  - Medical Research Council/United Kingdom
GR  - HHSN272200900046C/AI/NIAID NIH HHS/United States
GR  - R01 AI103341-01/AI/NIAID NIH HHS/United States
GR  - R01 AI103341/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Respir Crit Care Med
JT  - American journal of respiratory and critical care medicine
JID - 9421642
RN  - 0 (Porins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Female
MH  - Humans
MH  - Longitudinal Studies
MH  - Lung/*immunology
MH  - Male
MH  - Mice
MH  - Middle Aged
MH  - Porins/*immunology
MH  - Pseudomonas Infections/*immunology
MH  - Pseudomonas aeruginosa/*immunology
MH  - Sputum/immunology
MH  - T-Lymphocytes/*immunology
MH  - Young Adult
PMC - PMC4476516
OTO - NOTNLM
OT  - Pseudomonas
OT  - T lymphocyte
OT  - adaptive immunity
OT  - bronchiectasis
OT  - epitopes
EDAT- 2015/03/20 06:00
MHDA- 2015/08/19 06:00
PMCR- 2015/12/01
CRDT- 2015/03/20 06:00
PHST- 2015/03/20 06:00 [entrez]
PHST- 2015/03/20 06:00 [pubmed]
PHST- 2015/08/19 06:00 [medline]
PHST- 2015/12/01 00:00 [pmc-release]
AID - 10.1164/rccm.201411-1995OC [doi]
PST - ppublish
SO  - Am J Respir Crit Care Med. 2015 Jun 1;191(11):1250-64. doi: 
      10.1164/rccm.201411-1995OC.