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Rv3722c Promotes Mycobacterium tuberculosis Survival in Macrophages by Interacting With TRAF3
Yingying Lei1,2, Xiaojian Cao1,2, Weize Xu1,2
1State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.
Abstract:
Mycobacterium tuberculosis (M.tb) secretes numerous proteins to interfere with host immune response for its long-term survival. As one of the top abundant M.tb secreted proteins, Rv3722c was found to be essential for bacilli growth. However, it remains elusive how this protein interferes with the host immune response and regulates M.tb survival. Here, we confirmed that Rv3722c interacted with host TRAF3 to promote M.tb replication in macrophages. Knock-down of TRAF3 attenuated the effect of Rv3722c on the intracellular M.tb survival. The interaction between Rv3722c and TRAF3 hampered MAPK and NF-κB pathways, resulting in a significant increase of IFN-β expression and decrease of IL-1β, IL-6, IL-12p40, and TNF-α expression. Our study revealed that Rv3722c interacted with TRAF3 and interrupted its downstream pathways to promote M.tb survival in macrophages. These findings facilitate further understanding of the mechanism of M.tb secreted proteins in regulating the host cell immune response and promoting its intracellular survival.
Insights
Mycobacterium tuberculosis protein Rv3722c interacts with host TRAF3, promoting bacterial replication in macrophages. This interaction disrupts immune signaling, aiding tuberculosis survival.
Area of Science:
- Immunology
- Microbiology
- Molecular Biology
Background:
- Mycobacterium tuberculosis (M.tb) secretes proteins to evade host immunity.
- Rv3722c is an abundant M.tb secreted protein crucial for bacterial growth.
- The immune evasion mechanisms of Rv3722c remain largely unknown.
Purpose of the Study:
- To elucidate the role of Rv3722c in M.tb pathogenesis.
- To investigate the interaction between Rv3722c and host immune factors.
- To understand how Rv3722c contributes to M.tb survival within host cells.
Main Methods:
- Co-immunoprecipitation assays to confirm Rv3722c-TRAF3 interaction.
- Macrophage infection models with Rv3722c expression/knock-down.
- Western blotting and ELISA to analyze immune pathway activation and cytokine expression.
Main Results:
- Rv3722c directly interacts with host TNF receptor-associated factor 3 (TRAF3).
- Rv3722c binding to TRAF3 inhibits MAPK and NF-κB signaling pathways.
- This inhibition leads to increased IFN-β and decreased pro-inflammatory cytokines (IL-1β, IL-6, IL-12p40, TNF-α).
- TRAF3 knock-down reduces Rv3722c's ability to promote M.tb replication.
Conclusions:
- Rv3722c promotes M.tb intracellular survival by interacting with TRAF3.
- The Rv3722c-TRAF3 interaction dysregulates host immune responses.
- This study reveals a novel mechanism of M.tb immune evasion mediated by secreted proteins.
