Nanoparticles increase human bronchial epithelial cell susceptibility to respiratory syncytial virus infection via nerve growth factor‐induced autophagy
School of Medicine
Cytotoxic and neuroinflammatory effects of TiO2 nanoparticles (TiO2‐NP) in human airways are mediated by nerve growth factor (NGF), which is also implicated in the pathophysiology of respiratory syncytial virus (RSV) infection. We tested the hypothesis that exposure to TiO2‐NP results in increased susceptibility to RSV infection and exacerbation of airway inflammation via NGF‐mediated induction of autophagy in lower respiratory tract cells. Human primary bronchial epithelial cells were exposed to TiO2‐NP for 24 h prior to infection with recombinant red RSV (rrRSV). Expression of NGF and its TrkA and p75NTR receptors was measured by real‐time PCR and fluorescence‐activated cell sorting (FACS). Autophagy was assessed by beclin‐1 expression analysis. Cell death was studied by FACS after annexin V/propidium iodide staining. rrRSV infection efficiency more than doubled in human bronchial cells pre‐exposed to TiO2‐NP compared to controls. NGF and its TrkA receptor were upregulated in RSV‐infected bronchial cells pre‐exposed to TiO2‐NP compared to controls exposed to either rrRSV or TiO2‐NP alone. Silencing NGF gene expression with siRNA significantly inhibited rrRSV infection. rrRSV‐infected cells pre‐exposed to TiO2‐NP also showed increase in necrotic cell death and reduction in apoptosis, together with 4.3‐fold increase in expression of the early autophagosomal gene beclin‐1. Pharmacological inhibition of beclin‐1 by wortmannin resulted in increased apoptotic rate along with lower viral load. This study shows that TiO2‐NP exposure enhances the infectivity of RSV in human bronchial epithelial cells by upregulating the NGF/TrkA axis. The mechanism of this interaction involves induction of autophagy promoting viral replication and necrotic cell death.
Digital Commons Citation
Chakraborty, Sreeparna; Castranova, Vincent; Perez, Miriam K.; and Piedimonte, Giovanni, "Nanoparticles increase human bronchial epithelial cell susceptibility to respiratory syncytial virus infection via nerve growth factor‐induced autophagy" (2017). Faculty & Staff Scholarship. 1656.
Chakraborty, S., Castranova, V., Perez, M. K., & Piedimonte, G. (2017). Nanoparticles increase human bronchial epithelial cell susceptibility to respiratory syncytial virus infection via nerve growth factor-induced autophagy. Physiological Reports, 5(13), e13344. https://doi.org/10.14814/phy2.13344