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Destruction of self-derived PAMP via T3SS2 effector VopY to subvert PAMP-triggered immunity mediates Vibrio
Xuan Wu1, Lantian Zhou1, Chen Ye1
1Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China.
Abstract:
Cyclic di-guanosine monophosphate (c-di-GMP) is a unique bacterial second messenger but is hijacked by host cells during bacterial infection as a pathogen-associated molecular pattern (PAMP) to trigger STING-dependent immune responses. Here, we show that upon infection, VopY, an effector of Vibrio parahaemolyticus, is injected into host cells by type III secretion system 2 (T3SS2), a secretion system unique to its pathogenic strains and indispensable for enterotoxicity. VopY is an EAL-domain-containing phosphodiesterase and is capable of hydrolyzing c-di-GMP. VopY expression in host cells prevents the activation of STING and STING-dependent downstream signaling triggered by c-di-GMP and, consequently, suppresses type I interferon immune responses. The presence of VopY in V. parahaemolyticus enables it to cause both T3SS2-dependent enterotoxicity and cytotoxicity. These findings uncover the destruction of self-derived PAMPs by injecting specific effectors to suppress PAMP-triggered immune responses as a unique strategy for bacterial pathogens to subvert immunity and cause disease.
Insights
Vibrio parahaemolyticus uses VopY to destroy cyclic di-guanosine monophosphate (c-di-GMP), a host immune signal. This bacterial strategy suppresses immune responses, enabling infection and disease.
Area of Science:
- Microbiology
- Immunology
- Bacterial Pathogenesis
Background:
- Cyclic di-guanosine monophosphate (c-di-GMP) acts as a bacterial second messenger.
- Host cells recognize c-di-GMP as a pathogen-associated molecular pattern (PAMP) to activate STING-dependent immune responses.
- Bacterial pathogens have evolved mechanisms to evade host immunity.
Purpose of the Study:
- To investigate the role of Vibrio parahaemolyticus effector VopY in subverting host immunity.
- To understand how VopY interferes with c-di-GMP-mediated immune signaling.
- To elucidate the contribution of VopY to V. parahaemolyticus virulence.
Main Methods:
- Investigated VopY's phosphodiesterase activity against c-di-GMP.
- Assessed VopY's impact on STING activation and downstream signaling in host cells.
- Evaluated the role of VopY and type III secretion system 2 (T3SS2) in V. parahaemolyticus enterotoxicity and cytotoxicity.
Main Results:
- VopY, delivered by T3SS2, hydrolyzes host c-di-GMP.
- VopY inhibits STING activation and suppresses type I interferon responses.
- VopY contributes to both T3SS2-dependent enterotoxicity and cytotoxicity of V. parahaemolyticus.
Conclusions:
- V. parahaemolyticus employs VopY to degrade host c-di-GMP, a key immune-triggering molecule.
- Bacterial effector-mediated destruction of self-derived PAMPs is a novel immune evasion strategy.
- This mechanism facilitates bacterial pathogenesis by suppressing PAMP-triggered immunity.
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