Peptidoglycan recognition protein 4-deficiency enhances bacterial clearance of Streptococcus pneumoniae in mice

Streptococcus pneumoniae is the most frequent cause of community-acquired pneumonia. Endogenous host defense molecules such as PGLYRP4 might influence the course of this disease. PGLYRP4 primary expressed in epithelial cells and we could show, that it is downregulated in alveolar epithelial cells and upregulated in alveolar macrophages after stimulation with Streptococcus pneumoniae. Interestingly, mice lacking PGLYRP4 displayed an enhanced bacterial clearance in the lungs and fewer mice develop bacteremia. In addition, a higher recruitment of immune cells to the site of infection and an enhanced bacterial clearance by additionally stronger activation of phagocytes could be shown. This may depend on the higher expression of complement factors, interferon-associated genes and a higher proinflammatory cytokine response in PGLYRP4KO compared to wild type (wt) cells.This phenotype is underlined by changes in the complexity and composition of the caecal microbiota of PGLYRP4KO compared to wt mice as we show by 16S rRNA gene sequencing. Strikingly, we could proof, that the changes of the microbiota are responsible for the better clearance of S. pneumoniae lung infection by cohousing and stable transfer of the respective wt or PGLYRP4KO mice microbiota into germfree wt mice.