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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Cyclo(Phe-Pro) produced by the human pathogen Vibrio vulnificus inhibits host innate immune responses through the
Kiwan Kim1, Na-Jeong Kim1, So Young Kim1
1Department of Life Science, Sogang University, Seoul, South Korea.
Abstract:
Cyclo(Phe-Pro) (cFP) is a secondary metabolite produced by certain bacteria and fungi. Although recent studies highlight the role of cFP in cell-to-cell communication by bacteria, its role in the context of the host immune response is poorly understood. In this study, we investigated the role of cFP produced by the human pathogen Vibrio vulnificus in the modulation of innate immune responses toward the pathogen. cFP suppressed the production of proinflammatory cytokines, nitric oxide, and reactive oxygen species in a lipopolysaccharide (LPS)-stimulated monocyte/macrophage cell line and in bone marrow-derived macrophages. Specifically, cFP inhibited inhibitory κB (IκB) kinase (IKK) phosphorylation, IκBα degradation, and nuclear factor κB (NF-κB) translocation to the cell nucleus, indicating that cFP affects the NF-κB pathway. We searched for genes that are responsible for cFP production in V. vulnificus and identified VVMO6_03017 as a causative gene. A deletion of VVMO6_03017 diminished cFP production and decreased virulence in subcutaneously inoculated mice. In summary, cFP produced by V. vulnificus actively suppresses the innate immune responses of the host, thereby facilitating its survival and propagation in the host environment.
Insights
Cyclo(Phe-Pro) from Vibrio vulnificus suppresses host innate immunity by inhibiting the NF-κB pathway. This bacterial metabolite aids pathogen survival and propagation within the host environment.
Area of Science:
- Microbiology
- Immunology
- Molecular Biology
Background:
- Cyclo(Phe-Pro) (cFP) is a bacterial secondary metabolite with known roles in bacterial communication.
- The impact of cFP on host immune responses remains largely unexplored.
Purpose of the Study:
- To investigate the role of cFP produced by the human pathogen Vibrio vulnificus in modulating innate immune responses.
- To elucidate the molecular mechanisms by which cFP affects the host immune system.
Main Methods:
- Investigated cFP's effect on cytokine, nitric oxide, and reactive oxygen species production in LPS-stimulated macrophages.
- Analyzed the impact of cFP on the NF-κB signaling pathway, including IKK phosphorylation, IκBα degradation, and NF-κB translocation.
- Identified the gene responsible for cFP production in V. vulnificus (VVMO6_03017) and created a deletion mutant.
Main Results:
- cFP significantly suppressed proinflammatory cytokine production, nitric oxide, and reactive oxygen species in macrophages.
- cFP inhibited key components of the NF-κB pathway: IKK phosphorylation, IκBα degradation, and NF-κB nuclear translocation.
- Deletion of the VVMO6_03017 gene reduced cFP production and decreased V. vulnificus virulence in a mouse model.
Conclusions:
- Vibrio vulnificus-derived cFP actively suppresses host innate immune responses.
- cFP interferes with the NF-κB signaling pathway, facilitating pathogen survival and proliferation.
- The gene VVMO6_03017 is crucial for cFP production and contributes to V. vulnificus virulence.
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