Protective role of Haemophilus influenzae in Streptococcus pneumoniae-induced epithelium injury

Streptococcus pneumoniae is a major respiratory pathogen and a commensal bacterium of the nasopharynx. However, it remains unclear how commensal S. pneumoniae switches to a pathogenic form. Recently, a 3D human lung tissue model was established and adopted as a bacterial infection model. Here, we analysed the effects of commensal bacteria on the pathogenicity of S. pneumoniae in human tissues using a model constructed by interstitial layer of human fibroblasts mixed with collagen and an epithelial layer of layered human lung epithelial cells. When S. pneumoniae infected to the model, severe injury to the epithelial layer and interleukin-1β production were observed. Conversely, these inflammatory reactions were suppressed by co-infection with Haemophilus influenzae, without killing S. pneumoniae. Immunofluorescence staining showed that during co-infection, S. pneumoniae did not invade and remained on the surface of the epithelial layer. Notably, the suppression of epithelium injury was specifically attributed to the presence of H. influenzae, and the constant coexistence of both living bacteria was crucial for maintaining normal lung tissue. Conclusively, these findings indicate that a well-balanced coexistence of S. pneumoniae with H. influenzae and is essential for maintaining healthy lung tissues.