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Integrin-based diffusion barrier separates membrane domains enabling the formation of microbiostatic frustrated

Michelle E Maxson1, Xenia Naj2, Teresa R O'Meara3

  • 1Program in Cell Biology, Hospital for Sick Children, Toronto, Canada.

Elife
|March 20, 2018
PubMed

Insights

Macrophages engulf long Candida albicans hyphae into tubular phagosomes. A diffusion barrier forms, separating phagosome and cell membranes, enabling antimicrobial defense against fungal growth.

Area of Science:

  • Cell Biology
  • Immunology
  • Microbiology

Background:

  • Candida albicans hyphae can evade phagocytosis due to their large size.
  • Macrophages engulf portions of hyphae, forming incompletely sealed tubular phagosomes.

Purpose of the Study:

  • To investigate the membrane dynamics and barrier formation in phagosomes engulfing Candida albicans hyphae.
  • To understand the molecular mechanisms underlying the distinct lipid composition and separation of phagosomal and plasma membranes.

Main Methods:

  • Fluorescence microscopy
  • Lipid analysis
  • Fluorescence recovery after photobleaching (FRAP)
  • Investigating protein involvement (Syk, Pyk2/Fak, formin)

Main Results:

  • Frustrated phagosomes are stabilized by F-actin cuffs via integrin activation.
  • Distinct lipid compositions exist between the plasmalemma and phagosomal membrane (PtdIns(4,5)P2 absent in phagosome, PtdIns(3)P and PtdIns(3,4,5)P3 present).
  • A diffusion barrier forms, maintaining phagosome identity, dependent on Syk, Pyk2/Fak, and formin-mediated actin assembly.

Conclusions:

  • Macrophages generate specialized, distinct phagosomal compartments to contain Candida albicans hyphae.
  • The formation of a diffusion barrier and distinct lipid domains is crucial for deploying antimicrobial mechanisms and limiting fungal growth.
Keywords:
Candida albicanscell biologyintegrinsmacrophagephagocytosis

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