Underground railway particulate matter and susceptibility to pneumococcal infection

Miyashita, Lisa, Shears, Rebecca ORCID: https://orcid.org/0000-0002-0279-2801, Foley, Gary, Semple, Sean, Kadioglu, Aras and Grigg, Jonthan ORCID: https://orcid.org/0000-0003-3109-6028 (2022) Underground railway particulate matter and susceptibility to pneumococcal infection. eBioMedicine, 80. 104063. ISSN 2352-3964

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Abstract

Background: Concentrations of particulate matter less than 10 microns (PM10) on underground railways are higher than those near urban roads. Traffic-related PM10 increases pneumococcal infection via increasing the expression of platelet-activating factor receptor (PAFR), a receptor co-opted by pneumococci to adhere to cells. To date, it is unknown whether underground railway PM10 increases pneumococcal infection. This study sought to determine the effect of London Underground (LU) PM10 on; i) pneumococcal adhesion to airway cells, and ii) susceptibility to pneumococcal disease. Methods: A549 cells and human primary airway epithelial cells were cultured with 20 µg/mL PM10 from the Bakerloo (B-PM10) and Jubilee (J-PM10) line platforms of Baker Street station. PAFR expression was assessed by flow cytometry, and pneumococcal adhesion by colony forming unit (CFU) counts. Traffic-related PM10 was collected next to a main road near the station's entrance. The PAFR blocker CV3988 and the antioxidant N-acetyl cysteine were used to assess the role of PAFR-mediated pneumococcal adhesion and oxidative stress respectively. Pneumococcal infection of mice was done after exposure to 3×80 μg doses of intranasal LU-PM10. Findings: In A549 cells, human primary nasal cells, and human primary bronchial epithelial cells, B-PM10 and J-PM10 increased PAFR expression and pneumococcal adhesion. Stimulated adhesion was abrogated by CV3988 and N-acetyl cysteine. Traffic-related PM10 stimulated increased adhesion compared with B-PM10. B-PM10 and J-PM10 increased lung and blood CFU and mortality in mice. Treatment of B-PM10-exposed mice with CV3988 reduced blood CFU. Interpretation: LU-PM10 increases pneumococcal adhesion to airway cells and susceptibility to invasive disease in mice. Funding: The Medical College of Saint Bartholomew's Hospital Trust, and the UK Medical Research Council Programme Grant (MR/P011284/1).