Exposure to diesel exhaust particles increases susceptibility to invasive pneumococcal disease

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Shears, Rebecca K, Jacques, Laura C, Naylor, Georgia, Miyashita, Lisa, Shadia, Khandaker ORCID: 0000-0001-5084-9772, Lebre, Filipa, Lavelle, Ed C, Grigg, Johnathan, French, Neil ORCID: 0000-0003-4814-8293, Neill, Daniel R ORCID: 0000-0002-7911-8153 et al (show 1 more authors) and Kadioglu, Aras ORCID: 0000-0003-1137-6321 (2020) Exposure to diesel exhaust particles increases susceptibility to invasive pneumococcal disease. Journal of Allergy and Clinical Immunology, 145 (4). 1272-1284.e6.

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	Streptococcus pneumoniae, pneumococcus, pneumonia, pneumococcal disease, particulates, pollution
Depositing User:	Symplectic Admin
Date Deposited:	30 Jan 2020 12:42
Last Modified:	19 Jan 2023 00:05
DOI:	10.1016/j.jaci.2019.11.039
Open Access URL:	https://www.sciencedirect.com/science/article/pii/...
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3072683

Available Versions of this Item

• Exposure to diesel exhaust particles increases susceptibility to invasive pneumococcal disease. (deposited 30 Jan 2020 10:57)
  • Exposure to diesel exhaust particles increases susceptibility to invasive pneumococcal disease. (deposited 30 Jan 2020 12:42) [Currently Displayed]