PIKfyve mediates the maturation of mycobacteria-containing vesicles

Salomé Muñoz-Sánchez1, Michiel van der Vaart1, Annemarie H Meijer1

  • 1Institute of Biology Leiden, Leiden University, Leiden, Netherlands.

Insights

Phosphoinositide kinase, PIKfyve, is crucial for the host immune response against mycobacterial infections. Inhibiting PIKfyve impairs pathogen trafficking and autophagosome maturation, highlighting its role in cellular defense.

Area of Science:

  • Cell Biology
  • Immunology
  • Microbiology

Background:

  • Autophagosome-lysosome interactions are vital for degrading pathogens like mycobacteria.
  • Phosphoinositides (PtdIns) regulate pathogen trafficking within cellular degradation pathways.
  • PIKfyve kinase generates PtdIns(3,5)P2, essential for autophagosome maturation and lysosome function.

Purpose of the Study:

  • To investigate the role of PIKfyve in host defense against Mycobacterium marinum (Mm) infection.
  • To determine if PIKfyve activity influences the trafficking and degradation of Mm.

Main Methods:

  • Utilized zebrafish larvae infected with Mycobacterium marinum.
  • Employed chemical inhibitors (YM201636 and Apilimod) targeting PIKfyve enzymatic activity.
  • Analyzed vesicle trafficking, autophagy activation, and phagosome maturation in infected macrophages.

Main Results:

  • PIKfyve is essential for trafficking Mm-containing vesicles to degradative lysosomes.
  • PIKfyve inhibition disrupts autophagy pathway activation and (auto)phagosome maturation.
  • PIKfyve activity protects infected macrophages from cell death, enhancing the immune response.

Conclusions:

  • PIKfyve plays a significant role in the cellular immune defense against mycobacterial pathogens.
  • The study establishes a link between PIKfyve and the autolysosomal pathway's defense mechanisms against mycobacteria.

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