Actin and phosphoinositide recruitment to fully formed Candida albicans phagosomes in mouse macrophages

Sigrid E M Heinsbroek1, Lynn A Kamen, Philip R Taylor

  • 1Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.

Insights

Candida albicans yeast can survive inside macrophages by forming pseudohyphae. This study reveals dynamic actin localization and phosphoinositide signaling on these unique phagosomes, potentially aiding yeast escape from host cells.

Area of Science:

  • * Immunology and Microbiology
  • * Cell Biology and Host-Pathogen Interactions

Background:

  • * Candida albicans is a dimorphic yeast that invades macrophages (Mphi) through dectin-1.
  • * C. albicans can resist the phagosome environment, forming pseudohyphae and escaping Mphi.
  • * Understanding C. albicans phagosome dynamics is crucial for host defense mechanisms.

Purpose of the Study:

  • * To investigate the unique phagosomes formed by C. albicans within macrophages.
  • * To elucidate the role of actin polymerization and phosphoinositide signaling in C. albicans phagosome maturation.
  • * To determine the relationship between actin dynamics, phosphoinositides, and yeast escape from Mphi.

Main Methods:

  • * Microscopic analysis of actin localization and dynamics around C. albicans phagosomes.
  • * Detection of membrane phosphoinositides (PI(4,5)P(2), PI(3,4,5)P(3), PI(3,4)P(2), PI(3)P) on phagosomes.
  • * Inhibitor studies using PI3K inhibitors to assess actin polymerization independence.

Main Results:

  • * Actin localized dynamically around C. albicans phagosomes before disintegrating.
  • * Specific membrane phosphoinositides were found to localize to these phagosomes.
  • * Actin polymerization on C. albicans phagosomes was independent of PI3K signaling.

Conclusions:

  • * Mature C. albicans phagosomes exhibit dynamic actin polymerization.
  • * Phosphoinositide localization suggests complex signaling pathways involved.
  • * Actin polymerization on phagosomes may facilitate the escape of C. albicans from macrophages.