P. gingivalis-Induced TLR2 Interactome Analysis Reveals Association with PARP9.

Area of Science:

• Immunology
• Microbiology
• Cell Biology

Background:

• Porphyromonas gingivalis is a key bacterium in periodontal disease.
• Toll-like receptor 2 (TLR2) is crucial for host response but P. gingivalis exploits it for immune evasion via PI3K activation.

Purpose of the Study:

• To investigate the TLR2-dependent pathway used by P. gingivalis for immune escape.
• To identify proteins interacting with TLR2 during P. gingivalis infection.

Main Methods:

• Analysis of the TLR2 interactome in human macrophages using mass spectrometry after P. gingivalis infection or TLR2 agonist stimulation.
• Protein cross-linking, immunoprecipitation, and network analysis were employed.
• PARP9 knockdown was used to assess its functional role.

Main Results:

• Identified 792 interacting proteins, including poly (ADP-ribose) polymerase 9 (PARP9) and its complex members (DTX3L, NMI).
• PARP9 knockdown blocked type I interferon (IFN-I) production and reduced inflammatory cytokines in response to P. gingivalis.
• PARP9 mediates P. gingivalis-induced STAT1 phosphorylation and PI3K activation, impairing macrophage bactericidal activity.

Conclusions:

• PARP9 is a novel TLR2 interacting partner involved in P. gingivalis immune escape.
• PARP9 facilitates IFN-I induction and PI3K activation downstream of TLR2 sensing.
• Targeting the TLR2-PARP9 interaction may offer therapeutic strategies against P. gingivalis infections.