An Interaction of LPS and RSV Infection in Augmenting the AHR and Airway Inflammation in Mice
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ORIGINAL ARTICLE
An Interaction of LPS and RSV Infection in Augmenting the AHR and Airway Inflammation in Mice Na Zhou,1,2 Wei Li,1 Luo Ren,1 Xiaohong Xie,3 and Enmei Liu1,3,4
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 RSVinduced 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 RSVand 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. KEY WORDS: neutrophil; RSV; LPS; TRIF; MMP-9.
INTRODUCTION Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infection (LRTI) in children 1
Department of Respiratory Medicine, Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, CSTC2009CA5002, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China 2 Department of Pediatrics, The People’s Hospital of Bishan District, No. 82, Xinsheng Road, Bishan District, Chongqing, 402760, People’s Republic of China 3 Department of Respiratory Medicine, Children’s Hospital of Chongqing Medical University, No. 136, Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, People’s Republic of China 4 To whom correspondence should be addressed at Department of Respiratory Medicine, Children’s Hospital of Chongqing Medical University, No. 136, Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, People’s Republic of China. E-mail: [email protected]
under 5 years of age [1, 2], especially in infants with severe bronchiolitis, who require hospitalization and are at increased risk of developing recurrent wheezing or childhood asthma [3–5]. Cooper BS et al. [6] reported that coinfection of bacteria and viruses had a synergistic effect, leading to more se
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