The effect of air pollution on the transcriptomics of the immune response to respiratory infection

Daniel P Croft,Philip K Hopke,Augusto A Litonjua,Matthew N Mccall,Sally W Thurston,Carl J Johnston,Thomas J Mariani,David S Burton,Mark J Utell,David J Nagel,Steve N Georas,R Matthew Kottmann,David Q Rich,Soumyaroop Bhattacharya,Kelly Thevenet-Morrison,Ann R Falsey

doi:10.1038/s41598-021-98729-8

Daniel P Croft, Philip K Hopke + Show 14 more

Open Access

https://doi.org/10.1038/s41598-021-98729-8

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Abstract

Combustion related particulate matter air pollution (PM) is associated with an increased risk of respiratory infections in adults. The exact mechanism underlying this association has not been determined. We hypothesized that increased concentrations of combustion related PM would result in dysregulation of the innate immune system. This epidemiological study includes 111 adult patients hospitalized with respiratory infections who underwent transcriptional analysis of their peripheral blood. We examined the association between gene expression at the time of hospitalization and ambient measurements of particulate air pollutants in the 28 days prior to hospitalization. For each pollutant and time lag, gene-specific linear models adjusting for infection type were fit using LIMMA (Linear Models For Microarray Data), and pathway/gene set analyses were performed using the CAMERA (Correlation Adjusted Mean Rank) program. Comparing patients with viral and/or bacterial infection, the expression patterns associated with air pollution exposure differed. Adjusting for the type of infection, increased concentrations of Delta-C (a marker of biomass smoke) and other PM were associated with upregulation of iron homeostasis and protein folding. Increased concentrations of black carbon (BC) were associated with upregulation of viral related gene pathways and downregulation of pathways related to antigen presentation. The pollutant/pathway associations differed by lag time and by type of infection. This study suggests that the effect of air pollution on the pathogenesis of respiratory infection may be pollutant, timing, and infection specific.

Highlights

MethodsAs detailed in Falsey et al.[47], each patient was assigned an admitting diagnosis by a pulmonary specialist after examination of each subject and review of laboratory, microbiologic and radiographic data
All pollutants were associated with genes involved in protein folding, and all but Black carbon (BC) were associated with key iron homeostasis pathways
Our analysis suggests that while BC is associated with upregulation of type 1 interferon related pathway in the two weeks prior to infection, there may be a component of immune suppression associated with exposure to traffic pollution in the later lag periods

Summary

Methods

As detailed in Falsey et al.[47], each patient was assigned an admitting diagnosis by a pulmonary specialist after examination of each subject and review of laboratory, microbiologic and radiographic data. Subjects had comprehensive microbiologic testing and cases were adjudicated by specialists as viral alone, bacterial alone, or mixed viral-bacterial infection. From this population, 1–3 ml of peripheral whole blood RNA was collected from 118 patients in Tempus tubes and hybridized using an Illumina Human HT-12 v4 BeadChip kit. As 7 of the 118 patients had missing pollution data, we analyzed the data of 111 patients who had a transcriptional analysis of peripheral blood performed in our current study on the association between air pollution and gene expression

Results

Discussion

Conclusion