An Interaction of LPS and RSV Infection in Augmenting the AHR and Airway Inflammation in Mice

Abstract

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infection (LRTI) in children under 5 years of age, especially infants with severe bronchiolitis. Our preliminary clinical experiments showed that bacterial colonization was commonly observed in children with virus-induced wheezing, particularly in those with recurrent wheezing, suggesting that bacterial colonization with an accompanying viral infection may contribute to disease severity. In most cases, RSV-infected infants were colonized with pathogenic bacteria (mainly Gram-negative bacteria). LPS is the main component of Gram-negative bacteria and acts as a ligand for Toll-like receptor 4 (TLR4). Relevant studies have reported that the TLR family is crucial in mediating the link between viral components and immunologic responses to infection. Of note, TLR4 activation has been associated with disease severity during RSV infection. In the present study, we identified that LPS aggravated RSV-induced AHR and airway inflammation in BALB/c mice using an RSV coinfection model. We found that the airway inflammatory cells and cytokines present in BALF and TRIF in lung tissue play a role in inducing AHR and airway inflammation upon RSV and bacteria coinfection, which might occur through the TRIF-MMP-9-neutrophil-MMP-9 signalling pathway. These results may aid in the development of novel treatments and improve vaccine design.

Small Non-coding RNA Expression Following Respiratory Syncytial Virus or Measles Virus Infection of Neuronal Cells

“…These findings support how RSV may cause neurological irregularities in patients (Eisenhut, 2006;Li et al, 2006;Morichi et al, 2017). Several studies have described an association between lower respiratory tract RSV infection in infancy and the subsequent development of persistent wheezing in children (Zhou N. et al, 2017;Zhong et al, 2018). In mice, RSV induces long-term airway disease characterized by chronic airway inflammation and airway hyperreactivity (Long et al, 2016;Zhou N. et al, 2017), and RSV antigens have been detected in the lungs >100 days (Schwarze et al, 2004).…”

“…Several studies have described an association between lower respiratory tract RSV infection in infancy and the subsequent development of persistent wheezing in children (Zhou N. et al, 2017;Zhong et al, 2018). In mice, RSV induces long-term airway disease characterized by chronic airway inflammation and airway hyperreactivity (Long et al, 2016;Zhou N. et al, 2017), and RSV antigens have been detected in the lungs >100 days (Schwarze et al, 2004). However, RSV persistence does not appear in the bronchial epithelium (the primary site of viral replication) but in deeper lung structures (Long et al, 2016;Zhou N. et al, 2017).…”

“…In mice, RSV induces long-term airway disease characterized by chronic airway inflammation and airway hyperreactivity (Long et al, 2016;Zhou N. et al, 2017), and RSV antigens have been detected in the lungs >100 days (Schwarze et al, 2004). However, RSV persistence does not appear in the bronchial epithelium (the primary site of viral replication) but in deeper lung structures (Long et al, 2016;Zhou N. et al, 2017).…”

RSV Promotes Epithelial Neuroendocrine Phenotype Differentiation through NODAL Signaling Pathway

“…Next, the acute (7 d) and chronic (28 d) infection model of RSV infection was established by intranasal injection of RSV into guinea pigs [ 8 , 23 ]. We found that during the acute infection period (7 d), epithelial cells shed in the lung tissue, and a large number of inflammatory cells infiltrated in the microvessels.…”

Traditional Chinese medicine andrographolide sulfonate alleviates airway inflammation by supressing TRL3-TRIF in mice post respiratory syncytial virus infection

“…Other mice were administered intranasally with either andrographolide sulfonate at 20 µl (0.5 mg/mice/d) or normal saline on day 0 (2 h post-RSV infection) and days 1 to 4, consecutively. According to the previous data of the research group, it was found that the lung in ammation was most obvious on the 5th day after RSV infection in mice (Zhou et al, 2017). So all mice were sacri ced on day 5 post RSV infection.…”