Host HSPD1 Translocation from Mitochondria to the Cytoplasm Induced by <i>Streptococcus suis</i> Serovar 2 Enolase Mediates Apoptosis and Loss of Blood–Brain Barrier Integrity
Tong Wu,
Li Jia,
Siyu Lei,
Hexiang Jiang,
Jianan Liu,
Na Li,
Paul R. Langford,
Hongtao Liu,
Liancheng Lei
Affiliations
Tong Wu
State Key Laboratory for Zoonotic Diseases/Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China
Li Jia
State Key Laboratory for Zoonotic Diseases/Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China
Siyu Lei
School of Basic Medicine, Jilin University, Changchun 130021, China
Hexiang Jiang
State Key Laboratory for Zoonotic Diseases/Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China
Jianan Liu
State Key Laboratory for Zoonotic Diseases/Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China
Na Li
State Key Laboratory for Zoonotic Diseases/Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China
Paul R. Langford
Section of Paediatric Infectious Disease, Imperial College London, London W2 1NY, UK
Hongtao Liu
State Key Laboratory for Zoonotic Diseases/Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China
Liancheng Lei
State Key Laboratory for Zoonotic Diseases/Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China
Streptococcus suis serovar 2 (S. suis serovar 2) is a zoonotic pathogen that causes meningitis in pigs and humans, and is a serious threat to the swine industry and public health. Understanding the mechanism(s) by which S. suis serovar 2 penetrates the blood–brain barrier (BBB) is crucial to elucidating the pathogenesis of meningitis. In a previous study, we found that expression of the virulence factor enolase (Eno) by S. suis serovar 2 promotes the expression of host heat shock protein family D member 1 (HSPD1) in brain tissue, which leads to the apoptosis of porcine brain microvascular endothelial cells (PBMECs) and increased BBB permeability, which in turn promotes bacterial translocation across the BBB. However, the mechanism by which HSPD1 mediates Eno-induced apoptosis remains unclear. In this study, we demonstrate that Eno promotes the translocation of HSPD1 from mitochondria to the cytoplasm, where HSPD1 binds to β-actin (ACTB), the translocated HSPD1, and its interaction with ACTB led to adverse changes in cell morphology and promoted the expression of apoptosis-related proteins, second mitochondria-derived activator of caspases (Smac), and cleaved caspase-3; inhibited the expression of X-linked inhibitor of apoptosis protein (XIAP); and finally promoted cell apoptosis. These results further elucidate the role of HSPD1 in the process of Eno-induced apoptosis and increased BBB permeability, increasing our understanding of the pathogenic mechanisms of meningitis, and providing a framework for novel therapeutic strategies.
