Progranulin Plays a Protective Role in Pneumococcal Meningitis by Inhibiting Pyroptosis

Abstract

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.