Exposure to common respiratory bacteria alters the airway epithelial response to subsequent viral infection

Abstract

BackgroundColonization of the airways with potential pathogenic bacteria is observed in a number of chronic respiratory diseases, such as COPD or cystic fibrosis. Infections with respiratory viruses are known triggers of exacerbations of these diseases. We here investigated if pre-exposure to bacteria alters the response of lung epithelial cells to subsequent viral infection.MethodsBronchial epithelial cells (BEAS-2B cells and primary bronchial epithelial cells) were exposed to heat-inactivated Haemophilus influenzae, Pseudomonas aeruginosa or Streptococcus pneumoniae and subsequently infected with respiratory syncytial virus (RSV), type 2 human adenovirus or influenza B. Levels of pro-inflammatory cytokines, viral replication and expression of pattern recognition receptors were determined in culture supernatants and/or cell lysates.ResultsExposure of BEAS-2B cells to H. influenzae before and during RSV-infection synergistically increased the release of IL-6 (increase above calculated additive effect at 72 h: 56 % ± 3 %, mean ± SEM) and IL-8 (53 % ± 12 %). This effect was sustained even when bacteria were washed away before viral infection and was neither associated with enhanced viral replication, nor linked to increased expression of key pattern recognition receptors. P. aeruginosa enhanced the release of inflammatory cytokines to a similar extent, yet only if bacteria were also present during viral infection. S. pneumoniae did not enhance RSV-induced cytokine release. Surprisingly, adenovirus infection significantly reduced IL-6 release in cells exposed to either of the three tested bacterial strains by on average more than 50 %. Infection with influenza B on the other hand did not affect cytokine production in BEAS-2B cells exposed to the different bacterial strains.ConclusionPre-exposure of epithelial cells to bacteria alters the response to subsequent viral infection depending on the types of pathogen involved. These findings highlight the complexity of microbiome interactions in the airways, possibly contributing to the susceptibility to exacerbations and the natural course of airway diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0382-z) contains supplementary material, which is available to authorized users.

Nasopharyngeal Microbiome in Premature Infants and Stability during Rhinovirus Infection

“…This may have significant pathogenic consequences because exposure to common respiratory bacteria alters the airway epithelial response to subsequent viral infection. 34 …”

Viral–bacterial interactions in the respiratory tract

“…By doing so, the bacteria increase viral binding and replication of this type of virus in vitro (Gulraiz et al, 2015;Sajjan et al, 2006). Moreover, we have recently shown that H. influenzae and RSV can synergize in inducing the release of pro-inflammatory cytokines by respiratory epithelial cells (Bellinghausen et al, 2016). On the other hand, TLR3 expression, and consequently recognition of viral structures and antiviral type I/III IFN production, was shown to be impaired in bronchial epithelial cells exposed to Moraxella catarrhalis, another PPM commonly found in the LRT of COPD patients (Heinrich et al, 2016).…”

Disseminated adenovirus infection causing severe ARDS

“…In vitro studies have demonstrated the ability of H. influenzae to alter the respiratory epithelium and cause an exaggerated inflammatory response to a subsequent viral pathogen 23. There have also been data to suggest a synergistic effect between adenovirus and H. influenzae in respiratory infections 24 25.…”