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...

Full description

Saved in:
Bibliographic Details
Main Authors: Jingyao Wang, Lihua Kang, Wenlong Xu, Jiangming Xiao, Yajun Min, Sijie Li, Changlong Zhou, Yibing Yin, Xuemei Zhang, Qun Zhang
Format: Article
Language:English
Published: Wiley 2025-02-01
Series:Immunity, Inflammation and Disease
Subjects:
Online Access:https://doi.org/10.1002/iid3.70140
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2050-4527