Progranulin Plays a Protective Role in Pneumococcal Meningitis by Inhibiting Pyroptosis.

OBJECTIVE: Pneumococcal meningitis is a serious infectious disease with a high mortality rate and a global presence, and survivors have different degrees of neurological sequelae as a consequence of the host response to the infection. Progranulin (PGRN) is a multifunctional autocrine growth factor that is also a major immunoregulator. We want to investigate the role for PGRN in Pneumococcal meningitis in vivo and in vitro. METHOD: Mouse and cell models were established to explore the protective effect and mechanism of PGRN against pneumococcal meningitis. RESULTS: Progranulin plays a protective role in pneumococcal meningitis by inhibiting pyroptosis. Pyroptosis resulted from exposure of BV-2 cells to the bacterium and this was confirmed in the in vivo model. Administration of the NLRP3 inflammasome inhibitor MCC950 to mice prior to infection inhibited pyroptosis and protected PGRN -/- mice and BV-2 cell model from meningitis. CONCLUSION: This study implicates a protective role for PGRN in pneumococcal meningitis by inhibiting pyroptosis, indicating that PGRN may have therapeutic potential.