Pneumococcal proteins PspA and PspC induce CXCL8 production in human neutrophils: implications in pneumococcal infections

Surface-exposed pneumococcal virulence proteins pneumococcal surface protein A (PspA) and pneumococcal surface protein C (PspC) play important roles in the pathogenesis of invasive pneumococcal diseases. Human neutrophils are principle antimicrobial effector cells of the innate and adaptive immune systems. In this study, we investigated the effects of PspA and PspC on the up-regulation of chemokine CXCL8 in human neutrophils, and characterized the underlying intracellular signaling pathways. Both PspA and PspC were found to induce the release of newly synthesized CXCL8. Synergistic effect was observed in the combined treatment of PspA and PspC on the release of CXCL8. Products from PspA-deficient or PspC-deficient mutant pneumococcus that did not express PspA or PspC induced significantly less release of CXCL8 than wild type pneumococcus. Both PspA and PspC could activate p38 MAPK and NF-κB pathways in neutrophils, while inhibition of NF-κB and p38 MAPK could suppress the release of CXCL8 from neutrophils induced by PspA and PspC. Together, our results demonstrated that the induction of CXCL8 in human neutrophils activated by PspA and PspC was regulated by p38 MAPK and NF-κB pathways.