Document Detail

Immune mechanisms and the impact of the disrupted lung microbiome in chronic bacterial lung infection and bronchiectasis.
MedLine Citation:
PMID:  23286938     Owner:  NLM     Status:  MEDLINE    
Recent studies analysing immunogenetics and immune mechanisms controlling susceptibility to chronic bacterial infection in bronchiectasis implicate dysregulated immunity in conjunction with chronic bacterial infection. Bronchiectasis is a structural pathological end-point with many causes and disease associations. In about half of cases it is termed idiopathic, because it is of unknown aetiology. Bronchiectasis is proposed to result from a 'vicious cycle' of chronic bacterial infection and dysregulated inflammation. Paradoxically, both immune deficiency and excess immunity, either in the form of autoimmunity or excessive inflammatory activation, can predispose to disease. It appears to be a part of the spectrum of inflammatory, autoimmune and atopic conditions that have increased in prevalence through the 20th century, attributed variously to the hygiene hypothesis or the 'missing microbiota'. Immunogenetic studies showing a strong association with human leucocyte antigen (HLA)-Cw*03 and HLA-C group 1 homozygosity and combinational analysis of HLA-C and killer immunoglobulin-like receptors (KIR) genes suggests a shift towards activation of natural killer (NK) cells leading to lung damage. The association with HLA-DR1, DQ5 implicates a role for CD4 T cells, possibly operating through influence on susceptibility to specific pathogens. We hypothesize that disruption of the lung microbial ecosystem, by infection, inflammation and/or antibiotic therapy, creates a disturbed, simplified, microbial community ('disrupted microbiota') with downstream consequences for immune function. These events, acting with excessive NK cell activation, create a highly inflammatory lung environment that, in turn, permits the further establishment and maintenance of chronic infection dominated by microbial pathogens. This review discusses the implication of these concepts for the development of therapeutic interventions.
R J Boyton; C J Reynolds; K J Quigley; D M Altmann
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Clinical and experimental immunology     Volume:  171     ISSN:  1365-2249     ISO Abbreviation:  Clin. Exp. Immunol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-04     Completed Date:  2013-03-12     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  0057202     Medline TA:  Clin Exp Immunol     Country:  England    
Other Details:
Languages:  eng     Pagination:  117-23     Citation Subset:  IM    
Copyright Information:
© 2012 British Society for Immunology.
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MeSH Terms
Bacterial Infections / complications,  immunology*
Bronchiectasis / immunology*,  microbiology,  prevention & control
CD4-Positive T-Lymphocytes / immunology
Chronic Disease
Genetic Predisposition to Disease
HLA-C Antigens / genetics,  immunology
Killer Cells, Natural / immunology
Lung / immunology,  microbiology*
Lung Diseases / immunology,  microbiology
Metagenome / immunology*
Microbial Consortia
Polymorphism, Genetic
Receptors, KIR / genetics,  immunology
Grant Support
//Biotechnology and Biological Sciences Research Council; //Medical Research Council
Reg. No./Substance:
0/HLA-C Antigens; 0/Receptors, KIR

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