Attenuated Streptococcus pneumoniae vaccine candidate SPY1 promotes dendritic cell activation and drives a Th1/Th17 response

- SPY1 induces DCs activation with high levels of pro-inflammatory cytokines and co-stimulatory molecules.
- MAPK and NF-κB signaling pathways involved in SPY1 induced DCs activation.
- SPY1-activated DCs induce Th1 and Th17 response in vivo and in vitro.

Streptococcus pneumoniae is one of the causative agent of pneumonia, meningitis, otitis media and sepsis. Vaccination is an effective strategy to combat S. pneumoniae invasion. We previously reported that SPY1, a novel attenuated vaccine candidate against S. pneumoniae, induces a protective immune response against pneumococcal infection in mice. However, underlying mechanisms have yet to be fully illustrated. To explore the mechanism of innate and adaptive immunities induced by SPY1. In this study, bone marrow-derived dendritic cells (DCs) of mice were infected with SPY1 and its parental wild-type strain D39, SPY1-infected DCs were co-cultured with homologous CD4+T cells or adoptive transfer to C57BL/6 mice. Results showed that SPY1 promoted DCs maturation with increased levels of surface molecules such as CD40, CD86, and MHC II, and upregulated the expression of proinflammatory cytokines, including TNF-α, IL-6, IL-12p40, IL-12p70 and IL-23. By contrast, D39 did not efficiently induce DCs activation and maturation. SPY1 could also activate MAPK and NF-κB signaling pathways in DC, but D39 unlikely affected this pathways. SPY1 treated DCs also induced Th1 and Th17 responses in vitro and in vivo. Our results supported the potential of SPY1 as a novel attenuated pneumococcus vaccine, because SPY1-activated DCs exhibit fully matured phenotype, initiated an adaptive immune response, and orchestrated Th1 and Th17 responses.