Abstract
Nasal epithelial cells (NECs) are among the first cells to be exposed to air pollutants and respiratory viruses. Although it is known that air pollution exposure and rhinovirus infections increase the risk for asthma development independently, it is unclear how these risk factors interact on a cellular level. Therefore, we aimed to investigate how exposure to diesel particulate matter (DPM) modifies the response of primary NECs to rhinovirus (RV) infection in vitro. Exposure of re‐differentiated, primary NECs (49 healthy children [0–7 years], 12 adults) to DPM modified the mRNA expression of viral cell‐surface receptors, pattern recognition receptors, and pro‐inflammatory response (also protein levels). After exposure to DPM, we additionally infected the NECs with RV‐1b and RV‐16. Viral loads (assessed by titration assays) were significantly higher in DPM‐exposed compared with non‐exposed NECs. Exposure to DPM prior to RV infection resulted in a significant upregulation of pro‐inflammatory cytokines (mRNA and protein level) and β‐defensins mRNA, and significant downregulation of pattern recognition receptors mRNA and CXCL10 (mRNA and protein levels). There was no difference between all outcomes of NECs from children and adults. We can conclude that exposure to DPM prior to RV infection increases viral loads by downregulation of viral defense receptors and upregulation of pro‐inflammatory cytokines. Our findings indicate a strong interaction between air pollution and the antiviral response to RV infection in NECs. We provide mechanistic evidence that exposure to air pollution increases susceptibility to RV infection.
Highlights
Air pollution is associated with severe adverse health effects including oncological, cardiovascular, and respiratory diseases (Anderson et al, 2012; Liu & Grigg, 2018)
diesel particulate matter (DPM) exposure of re-d ifferentiated nasal epithelial cells (NECs) of children and adults decreased the levels of pattern recognition receptors (PRR) and CXCL10 and increased the levels of IL6, CXCL8, and IL1β
DPM exposure prior to RV-1 6 infection resulted in higher viral loads, lower expression of TLR3 and increased levels of IFN-β, IL1β, IL6, and CXCL8
Summary
Air pollution is associated with severe adverse health effects including oncological, cardiovascular, and respiratory diseases (Anderson et al, 2012; Liu & Grigg, 2018). Besides responding to environmental pollutants, another important role of respiratory epithelial cells is protection against viral infection and the regulation of immune responses and inflammation (Muller & Jaspers, 2012; Whitsett & Alenghat, 2015). RV infections are responsible for more than half of cold-like illnesses and are the most common causes of upper respiratory tract infections (Jacobs et al, 2013). They play a major role in respiratory morbidity, wheezing illnesses of children (Heymann et al, 2004; Kieninger et al, 2013; Korppi et al, 2004; Piotrowska et al, 2009), and asthma development and exacerbations (Jackson et al, 2008; Williams et al, 2021). Defensins (Proud et al, 2004), interferons (IFNs), and immune regulatory chemokines, and cytokines (e.g., C-X-C motif chemokine 10 [CXCL10], interleukin [IL] 1β, IL6 and CXCL8) are released and initiate the immune response (Yeo et al, 2010)
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