Air Pollution Exposure Impairs Airway Epithelium IFN-β Expression in Pre-School Children.

Matteo Bonato,Alberto Papi,Erica Bazzan,Simonetta Baraldo,Federico Baraldi,Marina Saetta,Elisa Gallo,Dario Gregori,Martina Turrin,Marco Contoli

doi:10.3389/fimmu.2021.731968

Matteo Bonato, Alberto Papi + Show 8 more

Open Access

https://doi.org/10.3389/fimmu.2021.731968

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Abstract

IntroductionAir pollution is a risk factor for respiratory infections and asthma exacerbations. We previously reported impaired Type-I and Type-III interferons (IFN-β/λ) from airway epithelial cells of preschool children with asthma and/or atopy. In this study we analyzed the association between rhinovirus-induced IFN-β/λ epithelial expression and acute exposure to the principal outdoor air pollutants in the same cohort.MethodsWe studied 34 children (17asthmatics/17non-asthmatics) undergoing fiberoptic bronchoscopy for clinical indications. Bronchial epithelial cells were harvested by brushing, cultured and experimentally infected with Rhinovirus Type 16 (RV16). RV16-induced IFN-β and λ expression was measured by quantitative real time PCR, as was RV16vRNA. The association between IFNs and the mean exposure to PM10, SO2 and NO2 in the day preceding bronchoscopy was evaluated using a Generalized Linear Model (GLM) with Gamma distribution.ResultsAcute exposure to PM10 and NO2 was negatively associated to RV16-induced IFNβ mRNA. For each increase of 1ug/m3 of NO2 we found a significative decrease of 2.3x103 IFN-β mRNA copies and for each increase of 1ug/m3 of PM10 a significative decrease of 1x103 IFN-β mRNA copies. No significant associations were detected between IFN-λ mRNA and NO2 nor PM10. Increasing levels of NO2 (but not PM10) were found to be associated to increased RV16 replication.ConclusionsShort-term exposure to high levels of NO2 and PM10 is associated to a reduced IFN-β expression by the airway epithelium, which may lead to increased viral replication. These findings suggest a potential mechanism underlying the link between air pollution, viral infections and asthma exacerbations.

Highlights

Air pollution is a risk factor for respiratory infections and asthma exacerbations
Aim of this study is to evaluate whether RV16 induced IFN-b and l messenger ribonucleic acid (RNA) (mRNA) levels were affected by the ambient air concentration of: i) nitrogen dioxide-(NO2), ii) particulate matter less than 10 μm in aerodynamic diameter (PM10) and iii) sulfur dioxide (SO2)
The study design and the population of the children cohort considered in this study has been previously described in Abbreviations: AHR, Aryl hydrocarbon receptor; ARPAV, Environmental Protection and Prevention Agency of Veneto Region; BAL, Bronchoalveolar lavage; BEBM, bronchial epithelial basal medium; BEGM, bronchial epithelial growth medium; HBEC, primary bronchial epithelial cells; ICS, inhaled corticosteroids; IgE, immunoglobulin E; IFN, interferon; NO2, nitrogen dioxide; mRNA, messenger RNA; PCR, polymerase chain reaction; PBS, phosphate buffered saline; PM10, particulate matter less than 10 μm in aerodynamic diameter; RNA, ribonucleic acid; RSV, respiratory syncytial virus; RTI, respiratory tract infections; RV16, rhinovirus type 16; SO2, sulfur dioxide; TCDD-inducible poly-ADPribose polymerase (TIPARP), TCDD-inducible poly-ADP-ribose polymerase; vRNA, viral RNA; WHO, world health organization

Summary

Introduction

Air pollution is a risk factor for respiratory infections and asthma exacerbations. We previously reported impaired Type-I and Type-III interferons (IFN-b/l) from airway epithelial cells of preschool children with asthma and/or atopy. Many studies have shown that the exposure to pollutants is associated to increased risk of respiratory viral infections, i.e. the most frequent triggers of asthma exacerbations, including rhinovirus, influenza and respiratory syncytial virus. The mechanisms by which air pollution may increase susceptibility to infections and favor viral-induced exacerbations in asthma patients are still largely unknown. We previously reported, impaired type I (IFN-b) and type III interferon (IFN-l) production following rhinovirus-16 (RV16) infection in bronchial epithelial cells of pre-school asthmatic and/or atopic children compared to non-asthmatic non-atopic children [3]. We reported that such impaired IFN response was associated to persistence of asthma symptoms up to school-age [4] in line with the epidemiological data suggesting that respiratory tract infections in childhood increase the risk of asthma

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