Japanese Flounder HMGB1: A DAMP Molecule That Promotes Antimicrobial Immunity by Interacting with Immune Cells and...

Area of Science:

• Immunology
• Marine Biology
• Molecular Biology

Background:

• High mobility group box (HMGB) proteins are crucial for DNA binding and chromosome structure.
• In mammals, HMGB proteins function as damage-associated molecular patterns (DAMPs) when released extracellularly under stress.
• The role of fish HMGB proteins as DAMPs during bacterial infections is largely unexplored.

Purpose of the Study:

• To investigate the immunological functions of HMGB1 and HMG20A in Japanese flounder.
• To determine if flounder HMGB proteins act as DAMPs during bacterial infection.
• To elucidate the mechanisms by which HMGB proteins contribute to antimicrobial immunity in fish.

Main Methods:

• Expression analysis of HMGB1 and HMG20A in Japanese flounder tissues.
• Investigation of HMGB1 release from peripheral blood leukocytes (PBLs) after bacterial challenge.
• Assessment of recombinant HMGB1's effects on PBLs, including ROS production and inflammatory gene expression.
• Evaluation of HMGB1 and HMG20A binding to bacterial pathogens and their role in bacterial agglutination.
• Analysis of HMGB1's impact on immune response and bacterial invasion during infection.

Main Results:

• HMGB1 and HMG20A were expressed in various flounder tissues.
• Bacterial challenge led to the release of HMGB1 from PBLs.
• Recombinant HMGB1 induced ROS production and inflammatory gene expression in PBLs.
• Both HMGB1 and HMG20A bound to bacterial pathogens, causing agglutination.
• HMGB1 enhanced PBL immune response and inhibited bacterial invasion during infection.

Conclusions:

• Flounder HMGB1 functions as a critical component of antimicrobial immunity.
• HMGB1 acts as both a modulator of immune cell activity and an extracellular DAMP that interacts with pathogens.
• These findings highlight the conserved role of HMGB proteins in innate immunity across vertebrates.