Immune induction identified by TMT proteomics analysis in Fusobacterium nucleatum autoinducer-2 treated macrophages

ABSTRACT

Background: The immune-inducing effect of the quorum sensing (QS) molecule autoinducer-2 (AI-2) on macrophages has not been previously comprehensively studied.

Methods: We performed proteomic analysis on macrophages cocultured with purified Fusobacterium nucleatum (F. nucleatum) AI-2 and performed western blot analysis to verify the differential protein expression. We further used the Gene Expression Profiling Interactive Analysis and Tumor Immune Estimation Resource databases to analyze the expression of differentially expressed proteins in microbial-associated digestive tract tumors.

Results: Based on proteomic analysis, we identified 46 upregulated proteins and 11 downregulated proteins. The upregulated proteins were mostly inflammatory factors such as tumor necrosis factor ligand superfamily member 9 (TNFSF9). These proteins have a range of biological functions associated with the regulation of inflammatory responses, apoptosis and tumorigenesis. TNFSF9 is highly expressed in pancreatic adenocarcinoma (PAAD) tissues and is associated with M1 polarization of macrophages.

Conclusions: Our data indicated that F. nucleatum AI-2 induced inflammatory responses and activated multiple signaling pathways in macrophages. TNFSF9 is the most significantly differentially expressed protein induced by F. nucleatum AI-2 and is involved in regulating immune cell infiltration in PAAD. Thus, AI-2 may become a new focus for studying the relationship between bacteria and cancer.

KEYWORDS:

• Autoinducer-2
• macrophages
• immune

Article highlights

• The quorum sensing signal molecule AI-2 can be sensed by the host immune system.

• Fusobacterium nucleatum mediates the development of digestive tract cancer by regulating the immune response.

• Proteomic analysis revealed that Fusobacterium nucleatum AI-2 induces macrophage inflammatory response and activates multiple signaling pathways.

• TNFSF9 is the most significantly differentially expressed protein induced by Fusobacterium nucleatum AI-2 and is involved in regulating immune cell infiltration in pancreatic adenocarcinoma and colon adenocarcinoma.

• TNFSF9 expression was significantly upregulated in pancreatic adenocarcinoma patients and was negatively correlated with overall survival.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.