Progranulin plays a protective role in pneumococcal meningitis by inhibiting pyroptosis

Bacterial meningitis is a serious infectious disease with a high mortality rate and a global presence. Streptococcus pneumoniae is a primary etiologic agent of this disease 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 investigated a role for PGRN in bacterial meningitis in vivo with PGRN -/- mice and in vitro with the mouse microglioma cell line BV-2. 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. This study implicates a protective role for PGRN in pneumococcal meningitis by inhibiting pyroptosis.