Streptococcus pneumoniae is a Gram-positive pathogen with
high morbidity and mortality globally but some of its pathogenesis
remains unknown. Previous research has provided
evidence that aminopeptidase N (PepN) is most likely a virulence
factor of S. pneumoniae. However, its role in S. pneumoniae
virulence and its interaction with the host remains
to be confirmed. We generated a pepN gene deficient mutant
strain and found that its virulence for mice was significantly
attenuated as were in vitro adhesion and invasion of host
cells. The PepN protein could induce a strong innate immune
response in vivo and in vitro and induced secretion of IL-6
and TNF-α by primary peritoneal macrophages via the rapid
phosphorylation of MAPK and PI3K/AKT signaling pathways
and this was confirmed using specific pathway inhibitors.
In conclusion, PepN is a novel virulence factor that is
essential for the virulence of S. pneumoniae and induces host
innate immunity via MAPK and PI3K/AKT signaling.
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