PMC:7025480 / 27524-30618
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7025480","sourcedb":"PMC","sourceid":"7025480","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7025480","text":"We infected human bronchial epithelial cells (BEAS2B and human primary bronchial epithelial cells) with RSV or hRV in the presence of P. aeruginosa conditioned medium. We used conditioned medium to analyze soluble, secreted factors from P. aeruginosa that might interfere with sensitivity to virus infection. Preliminary experiments (data not shown) indicate that also infection with live P. aeruginosa results in inhibition of type III IFN activity and thus recapitulates the effects with conditioned medium. We observed that PAO1 was able to suppress the antiviral response of bronchial epithelial cells toward respiratory viruses (RSV and hRV) which subsequently lead to higher virus titers in secondary infected cells. Due to the stronger effects observed with RSV we subsequently focused on RSV modulation, but findings were similar for hRV (Figures S3–S5). Interestingly, P. aeruginosa strain Boston, a control strain frequently used in Pseudomonas research was not able to modulate the antiviral response. Due to genetic heterogeneity, P. aeruginosa can be divided into three phylogroups (25). Using representative strains of each group (PAO1—group 1; PA14—group 2; PA7—group 3) we observed that only the minor group 3 strain PA7 was not able to modulate the antiviral response, whereas PA14 could, a clone for which global spread has been shown (25, 30). These findings indicate that most of the P. aeruginosa strains found in the environment and causing infections in CF patients are able to modulate the antiviral response since most of P. aeruginosa isolates are of group 1 or group 2. Two earlier studies could also demonstrate that P. aeruginosa is able to modulate the antiviral response of epithelial cells (31, 32). In addition, the first study could demonstrate a difference in virus-induced IFN expression between healthy and CF-derived cells. However, we and the second study did not observe differences in IFN induction. In line with our results, a third study also failed to detect a difference of virus-induced IFN production between healthy and CF-derived epithelial cells (33). Therefore, our observations might also be relevant in diseases where chronic P. aeruginosa infections occur and a role of respiratory viruses in pulmonary exacerbations has been established, e.g., COPD (34). We have not analyzed whether such modulatory activities are also realized in other lung pathogens, but so far the here identified mechanisms are only reported for P. aeruginosa. It has been reported that P. aeruginosa PAK1 infection in a mouse model can induce IFNλ which promotes an inflammatory response and has a negative impact on P. aeruginosa defense in vivo (35). Of note, PAK1 compared to PAO1 has a point mutation in LasR which might affect protease activity (36). Moreover, the PAK strain induced IFNβ in airway epithelial cells, but CF epithelial cells showed a reduced response compared to healthy cells (37). However, so far it had not been reported that CF epithelial cells display increased sensitivity toward viral infection (38) which was the main focus of our 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