Cofilin regulator 14-3-3zeta is an evolutionarily conserved protein required for phagocytosis and microbial

Johanna Ulvila1, Leena-Maija Vanha-aho, Anni Kleino

  • 1Departments of Pediatrics, Biocenter Oulu, University of Oulu, Finland.

Insights

This study identifies key genes, including 14-3-3ζ, that mediate bacterial phagocytosis in Drosophila. The protein 14-3-3ζ is crucial for host defense and microbial resistance across insects and vertebrates.

Area of Science:

  • Cell Biology
  • Immunology
  • Genetics

Background:

  • Phagocytosis is a fundamental cellular process vital for host defense against pathogens.
  • In Drosophila melanogaster, hemocytes act as phagocytic, macrophage-like cells to engulf microbes.

Purpose of the Study:

  • To identify novel mediators of bacterial phagocytosis using an RNAi-based screen in Drosophila.
  • To investigate the evolutionary conservation and functional role of identified mediators in host defense.

Main Methods:

  • Conducted an RNAi-based in vitro screen in Drosophila S2 hemocyte cell line.
  • Validated the role of 14-3-3ζ in primary Drosophila hemocytes and in zebrafish and mouse models.
  • Assessed microbial resistance in Drosophila and zebrafish infection models.

Main Results:

  • Identified Abi, cpa, 14-3-3ζ, tlk, CG2765, and CG15609 as mediators of bacterial phagocytosis.
  • Demonstrated an evolutionarily conserved role for 14-3-3ζ in phagocytosis across Drosophila, zebrafish, and mouse cells.
  • Showed that 14-3-3ζ is essential for resistance against Staphylococcus aureus infections in vivo.

Conclusions:

  • 14-3-3ζ is a critical mediator of bacterial phagocytosis.
  • 14-3-3ζ plays an essential role in microbial resistance in both insects and vertebrates, highlighting its conserved function in innate immunity.

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