Exposure to diesel particulate matter enhances the rhinovirus load in primary nasal epithelial cells

Abstract

Nasal epithelial cells (NECs) are among the first cells to be exposed to air pollutants and respiratory viruses. They act as a “switchboard” to initiate and regulate immune responses. While it is known that air pollution exposure and rhinovirus (RV) infections increase the risk for asthma development, it is unclear how these risk factors interact on a cellular level. Therefore, we studied how exposure to diesel particulate matter (DPM) modifies the response of NECs to RV infections. Re-differentiated NECs of 10 healthy, adult volunteers were sprayed with DPM. 4hrs later, NECs were infected with RV-16 (multiplicity of infection (MOI)=1 or 4). NECs were harvested 20hrs later and analyzed for viral load and mRNA expression of different genes by quantitative RT-PCR. DPM exposure previous to RV infection increased the viral load and RV-16 mRNA levels in NECs. NECs infected with MOI=1 of RV-16 had a 50% tissue culture infective dose (TCID50) median of 6.3x10² (99% confidence interval (CI)=6.3x10²-6.3x10⁶), compared to 6.3x10⁴ (CI=6.3x10²-6.3x10⁷) after DPM exposure. RV-16 infection with MOI=4 had a TCID50 median of 6.3x10³ (CI=6.3x10²-6.3x10⁷), compared to 6.3x10⁴ (CI=6.3x10³-6.3x10⁷) after DPM exposure. DPM exposure previous to RV infection increased RV-16 mRNA levels 1.5fold (SD 0.29) for MOI=1, and 5.7fold (SD 2.6) for MOI=4, respectively, compared to infection only (n=3). Preliminary results of mRNA expression showed a trend of increased IFN-β and -λ in NECs exposed to DPM previous to RV infection with MOI=4, but not MOI=1 (n=3). DPM exposure prior to RV infection increases the viral load and may change the anti-viral NEC response, indicating adverse effects of air pollution exposure.