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Autoinducer-2 of Fusobacterium nucleatum promotes macrophage M1 polarization via TNFSF9/IL-1β signaling

Jiao Wu1, Kang Li2, Wei Peng1

  • 1Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Sichuan 646000, China.

International Immunopharmacology
|July 5, 2019
PubMed

Insights

Fusobacterium nucleatum autoinducer-2 (AI-2) enhances macrophage mobility and M1 polarization via the TNFSF9/IL-1β pathway. This finding suggests AI-2 as a potential target for treating gut microbiota-related diseases.

Area of Science:

  • Microbiology
  • Immunology
  • Oncology

Background:

  • The role of Fusobacterium nucleatum autoinducer-2 (AI-2) in macrophage polarization remains unclear.
  • Understanding AI-2's impact on immune cells is crucial for deciphering gut microbiota-related diseases.

Purpose of the Study:

  • To investigate the effect of F. nucleatum AI-2 on macrophage migration and polarization.
  • To elucidate the underlying molecular mechanisms, including specific signaling pathways.
  • To evaluate the relevance of these findings in human colorectal cancer (CRC).

Main Methods:

  • Utilized cultured macrophages to assess migration and polarization.
  • Employed quantitative proteomics to identify AI-2-interacting proteins.
  • Analyzed the expression of TNFSF9/TRAF1/p-AKT/IL-1β signaling in vitro and in human CRC tissues.

Main Results:

  • F. nucleatum AI-2 significantly enhanced macrophage mobility and M1 polarization.
  • The TNFSF9/TRAF1/p-AKT/IL-1β signaling pathway was implicated in AI-2-mediated effects.
  • Elevated TNFSF9 and IL-1β expression was observed in human CRCs, correlating with AI-2 levels and improved survival.

Conclusions:

  • AI-2 induces M1 polarization of macrophages by activating the TNFSF9/IL-1β pathway.
  • AI-2 represents a potential therapeutic target for immunotherapy in gut microbiota-associated diseases.
  • Targeting AI-2 may offer novel strategies for colorectal cancer treatment.
Keywords:
Autoinducer-2Colorectal cancerFusobacterium nucleatumGut microbiotaMacrophages

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