Immune deficiencies, infection, and systemic immune disorders
Adhesion of Streptococcus pneumoniae to human airway epithelial cells exposed to urban particulate matter

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Background

Epidemiologic studies report an association between pneumonia and urban particulate matter (PM) less than 10 microns (μm) in aerodynamic diameter (PM10). Streptococcus pneumoniae is a common cause of bacterial pneumonia worldwide. To date, the mechanism whereby urban PM enhances vulnerability to S pneumoniae infection is unclear. Adhesion of S pneumoniae to host cells is a prerequisite for infection. Host-expressed proteins, including the receptor for platelet-activating factor (PAFR), are co-opted by S pneumoniae to adhere to lower airway epithelial cells.

Objectives

To define whether inhalable urban PM enhances the adhesion of S pneumoniae to airway epithelial cells.

Methods

A549 cells were cultured with PM10 from Leicester (United Kingdom [UK]) and PM10 and PM less than 2.5 μm in aerodynamic diameter (PM2.5) from Accra (Ghana), then infected with S pneumoniae strain D39. Pneumococcal adhesion to human primary bronchial epithelial cells was also assessed. Bacterial adhesion was determined by quantitative culture and confocal microscopy. The role of oxidative stress was assessed by N-acetyl cysteine, and the role of PAFR was assessed by mRNA transcript level, receptor expression, and receptor blocking.

Results

PM10 (UK) increased S pneumoniae adhesion to both A549 airway epithelial cells and human primary bronchial epithelial cells. PM10 (Ghana) and PM2.5 (Ghana) also increased adhesion. Culture of A549 cells by PM10 (UK) increased PAFR mRNA transcript level and PAFR expression. PM10 (UK)–stimulated adhesion to A549 cells was attenuated by a PAFR blocker and N-acetyl cysteine.

Conclusion

Urban PM increases adhesion of S pneumoniae to human airway epithelial cells. PM-stimulated adhesion is mediated by oxidative stress and PAFR.

Section snippets

Cells and S pneumoniae

A549, a human type II pneumocyte cell line, was obtained from Sigma-Aldrich (Poole, Dorset, United Kingdom [UK]) and maintained in Dulbecco modified Eagle medium (Invitrogen Ltd, Paisley, UK) with 10% FBS and 1% L-glutamine/penicillin-streptomycin (Lonza Ltd, Basel, Switzerland). Human primary bronchial epithelial cells (HBEpC) were obtained from the main bronchi of a  healthy white male and were purchased from Promocell (Heidelberg, Germany). The virulent type 2 S pneumoniae encapsulated

Results

Culture of A549 cells with urban PM10 (UK) increased adhesion of S pneumoniae assessed by quantitative culture (P < .001 vs medium control at 50 μg/mL; Fig 1). Confocal microscopy of fluorescent S pneumoniae confirmed that PM10 (UK) stimulated a dose-dependent increase in pneumococcal adhesion to A549 cells (P < .01 vs medium control; Fig 2). Increased pneumococcal adhesion to A549 cells resulted in increased intracellular penetration of bacteria (P < .01; Fig 3). The same pattern of adhesion

Discussion

In this study, we found that inhalable PM from urban areas in both the developing world and the developed world increases the adhesion of pneumococci to human airway epithelial cells. Pneumococcal adhesion stimulated by urban PM is associated with enhanced vulnerability to cellular infection. We excluded the possibility that increased pneumococcal adhesion is due to cell death or injury by the absence of LDH release and MTT expression. Electron microscopy of PM-exposed cells showed PM attached

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    Supported by Queen Mary University London.

    Disclosure of potential conflict of interest: M. Ezzati receives research support from the US National Science Foundation. The rest of the authors have declared that they have no conflict of interest.

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