Cytosolic MtDNA Released from Pneumolysin-Damaged Mitochondria Triggers IFN-beta Production in Epithelial Cells.

Pneumolysin (Ply) is a major virulence factor of Streptococcus pneumoniae (S. pn). It has been proved Ply induced interferon-beta (IFN-beta) expression in host macrophages that is down to the accumulation of mitochondrial deoxyribonucleic acid (mtDNA) in the cytoplasm during S. pn infection. Our findings extend this work to show human bronchial epithelial cells which exist at the interface of inflammatory injury, BEAS-2B, adapt to local cues by altering mitochondrial states and excessive release of mtDNA. The results in this research showed that purified Ply induced the expression of IFN-beta in human epithelial cells, which was accompanied by mitochondrial damage both in vivo and in vitro. The observations also were supported by the increased mtDNA concentrations in the bronchial lavage fluid (BALF) of S. pn infected mice. In summary, our study demonstrated that Ply triggered the production of IFN-beta in epithelial cells and this response was mediated by mtDNA released from Ply-damaged mitochondria. It displayed an impressive modulation of IFN-beta response to S. pn in epithelial cells.