Exposure to diesel exhaust particles increases susceptibility to invasive pneumococcal disease.


Journal

The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002

Informations de publication

Date de publication:
04 2020
Historique:
received: 01 08 2019
revised: 07 11 2019
accepted: 08 11 2019
pubmed: 28 1 2020
medline: 26 1 2021
entrez: 28 1 2020
Statut: ppublish

Résumé

The World Health Organization estimates that air pollution is responsible for 7 million deaths per annum, with 7% of these attributable to pneumonia. Many of these fatalities have been linked to exposure to high levels of airborne particulates, such as diesel exhaust particles (DEPs). We sought to determine whether exposure to DEPs could promote the progression of asymptomatic nasopharyngeal carriage of Streptococcus pneumoniae to invasive pneumococcal disease. We used mouse models and in vitro assays to provide a mechanistic understanding of the link between DEP exposure and pneumococcal disease risk, and we confirmed our findings by using induced sputum macrophages isolated from healthy human volunteers. We demonstrate that inhaled exposure to DEPs disrupts asymptomatic nasopharyngeal carriage of S pneumoniae in mice, leading to dissemination to lungs and blood. Pneumococci are transported from the nasopharynx to the lungs following exposure to DEPs, leading to increased proinflammatory cytokine production, reduced phagocytic function of alveolar macrophages, and consequently, increased pneumococcal loads within the lungs and translocation into blood. These findings were confirmed by using DEP-exposed induced sputum macrophages isolated from healthy volunteers, demonstrating that impaired innate immune mechanisms following DEP exposure are also at play in humans. Lung inhaled DEPs increase susceptibility to pneumococcal disease by leading to loss of immunological control of pneumococcal colonisation, increased inflammation, tissue damage, and systemic bacterial dissemination.

Sections du résumé

BACKGROUND
The World Health Organization estimates that air pollution is responsible for 7 million deaths per annum, with 7% of these attributable to pneumonia. Many of these fatalities have been linked to exposure to high levels of airborne particulates, such as diesel exhaust particles (DEPs).
OBJECTIVES
We sought to determine whether exposure to DEPs could promote the progression of asymptomatic nasopharyngeal carriage of Streptococcus pneumoniae to invasive pneumococcal disease.
METHODS
We used mouse models and in vitro assays to provide a mechanistic understanding of the link between DEP exposure and pneumococcal disease risk, and we confirmed our findings by using induced sputum macrophages isolated from healthy human volunteers.
RESULTS
We demonstrate that inhaled exposure to DEPs disrupts asymptomatic nasopharyngeal carriage of S pneumoniae in mice, leading to dissemination to lungs and blood. Pneumococci are transported from the nasopharynx to the lungs following exposure to DEPs, leading to increased proinflammatory cytokine production, reduced phagocytic function of alveolar macrophages, and consequently, increased pneumococcal loads within the lungs and translocation into blood. These findings were confirmed by using DEP-exposed induced sputum macrophages isolated from healthy volunteers, demonstrating that impaired innate immune mechanisms following DEP exposure are also at play in humans.
CONCLUSION
Lung inhaled DEPs increase susceptibility to pneumococcal disease by leading to loss of immunological control of pneumococcal colonisation, increased inflammation, tissue damage, and systemic bacterial dissemination.

Identifiants

pubmed: 31983527
pii: S0091-6749(19)31635-5
doi: 10.1016/j.jaci.2019.11.039
pmc: PMC7154500
pii:
doi:

Substances chimiques

Particulate Matter 0
Vehicle Emissions 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1272-1284.e6

Subventions

Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P011284/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 204457/Z/16/Z
Pays : United Kingdom

Informations de copyright

Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.

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Auteurs

Rebecca K Shears (RK)

Bacterial Pathogenesis and Immunity Group, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.

Laura C Jacques (LC)

Bacterial Pathogenesis and Immunity Group, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.

Georgia Naylor (G)

Bacterial Pathogenesis and Immunity Group, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.

Lisa Miyashita (L)

Centre for Genomics and Child Health, Blizard Institute, Queen Mary University of London, London, United Kingdom.

Shadia Khandaker (S)

Bacterial Pathogenesis and Immunity Group, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.

Filipa Lebre (F)

Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.

Ed C Lavelle (EC)

Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.

Jonathan Grigg (J)

Centre for Genomics and Child Health, Blizard Institute, Queen Mary University of London, London, United Kingdom.

Neil French (N)

Bacterial Pathogenesis and Immunity Group, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.

Daniel R Neill (DR)

Bacterial Pathogenesis and Immunity Group, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom; Microbial Evolution, Genomics and Adaptation Group, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.

Aras Kadioglu (A)

Bacterial Pathogenesis and Immunity Group, Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom. Electronic address: A.Kadioglu@liverpool.ac.uk.

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