HP1330 Contributes to Streptococcus suis Virulence by Inducing Toll-Like Receptor 2- and ERK1/2-Dependent Pro-inflammatory Responses and Influencing In Vivo S. suis Loads

• Published in: Frontiers in immunology Vol. 8; p. 869
• Main Authors: Zhang, Qiang, Huang, Jingjing, Yu, Junping, Xu, Zhongmin, Liu, Liang, Song, Yajing, Sun, Xiaomei, Zhang, Anding, Jin, Meilin
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 31.07.2017
• Subjects: excessive inflammation; Immunology; recognition receptor; signaling pathway; streptococcal toxic shock-like syndrome; Streptococcus suis 2; streptococcal toxic shock-like syndrome; signaling pathway; recognition receptor; excessive inflammation; Streptococcus suis 2
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2017.00869

2 (SS2) has evolved into a highly invasive pathogen responsible for two large-scale outbreaks of streptococcal toxic shock-like syndrome (STSLS) in China. Excessive inflammation stimulated by SS2 is considered a hallmark of STSLS, even it also plays important roles in other clinical symptoms of SS2-related disease, including meningitis, septicemia, and sudden death. However, the mechanism of SS2-caused excessive inflammation remains poorly understood. Here, a novel pro-inflammatory protein was identified (HP1330), which could induce robust expression of pro-inflammatory cytokines (TNF-α, MCP-1, and IL-1β) in RAW264.7 macrophages. To evaluate the role of HP1330 in SS2 virulence, an deletion mutant ( ) was constructed. disruption led to a decreased pro-inflammatory ability of SS2 in RAW 264.7 macrophages. showed reduced lethality, pro-inflammatory activity, and bacterial loads in mice. To further elucidate the mechanism of HP1330-induced pro-inflammatory cytokine production, antibody blocking and gene-deletion experiments with macrophages were performed. The results revealed that the pro-inflammatory activity of HP1330 depended on the recognition of toll-like receptor 2 (TLR2). Furthermore, a specific inhibitor of the extracellular signal-regulated kinase 1/2 (ERK1/2) pathways could significantly decrease HP1330-induced pro-inflammatory cytokine production, and western blot analysis showed that HP1330 could induce activation of the ERK1/2 pathway. Taken together, our findings demonstrate that HP1330 contributes to SS2 virulence by inducing TLR2- and ERK1/2-dependent pro-inflammatory cytokine production and influencing bacterial loads, implying that HP1330 may be associated with STSLS caused by SS2.