title: Toll-like receptor 4 confers inflammatory response to Suilysin.
abstract: Streptococcus suis serotype 2 (SS2) is an emerging human pathogen worldwide. A large outbreak occurred in the summer of 2005 in China. Serum samples from this outbreak revealed that levels of the main proinflammatory cytokines were significantly higher in patients with streptococcal toxic-shock-like syndrome (STSLS) than in patients with meningitis only. However, the mechanism underlying the cytokine storm in STSLS caused by SS2 remained unclear. In this study, we found that suilysin (SLY) is the main protein inflammatory stimulus of SS2 and that native SLY (nSLY) stimulated cytokines independently of its haemolytic ability. Interestingly, a small amount of SLY (Å Mol/L) induced strong, long-term TNF-α release from human PBMCs. We also found that nSLY stimulated TNF-α in wild-type macrophages but not in macrophages from mice that carried a spontaneous mutation in TLR4 (P712H). We demonstrated for the first time that SLY stimulates immune cells through TLR4. In addition, the Myd88 adaptor-p38-MAPK pathway was involved in this process. The present study suggested that the TLR4-dependent inflammatory responses induced by SLY in host might contribute to the STSLS caused by SS2 and that p38-MAPK could be used as a target to control the release of excess TNF-α induced by SS2.
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology Beijing, China ; Beijing Key Laboratory of Immunology Regulatory and Organ Transplantation, Basic Research Lab of Organ Transplant Institute, 309th Hospital of the People's Liberation Army Beijing, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Bi
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology Beijing, China.
authors.forename: Yaya
authors.initials: Y
authors.lastname: Pian
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology Beijing, China.
authors.forename: Shaolong
authors.initials: S
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology Beijing, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology Beijing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology Beijing, China.
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Lv
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology Beijing, China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology Beijing, China.
authors.forename: Shengwei
authors.initials: S
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Science Beijing, China.
authors.forename: Huaijie
authors.initials: H
authors.lastname: Hao
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology Beijing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology Beijing, China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Jiang
keywords: MAPK; SLY; TLR4; inflammation