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

  1. Michelle E Maxson
  2. Xenia Naj
  3. Teresa R O'Meara
  4. Jonathan D Plumb
  5. Leah E Cowen
  6. Sergio Grinstein  Is a corresponding author
  1. The Hospital for Sick Children, Canada
  2. University Medical Center Hamburg-Eppendorf, Germany
  3. University of Toronto, Canada

Abstract

Candida albicans hyphae can reach enormous lengths, precluding their internalization by phagocytes. Nevertheless, macrophages engulf a portion of the hypha, generating incompletely sealed tubular phagosomes. These frustrated phagosomes are stabilized by a thick cuff of F-actin that polymerizes in response to non-canonical activation of integrins by fungal glycan. Despite their continuity, the surface and invaginating phagosomal membranes retain a strikingly distinct lipid composition. PtdIns(4,5)P2 is present at the plasmalemma but is not detectable in the phagosomal membrane, while PtdIns(3)P and PtdIns(3,4,5)P3 co-exist in the phagosomes yet are absent from the surface membrane. Moreover, endo-lysosomal proteins are present only in the phagosomal membrane. Fluorescence recovery after photobleaching revealed the presence of a diffusion barrier that maintains the identity of the open tubular phagosome separate from the plasmalemma. Formation of this barrier depends on Syk, Pyk2/Fak and formin-dependent actin assembly. Antimicrobial mechanisms can thereby be deployed, limiting the growth of the hyphae.

Article and author information

Author details

  1. Michelle E Maxson

    Program in Cell Biology, The Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Xenia Naj

    Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Teresa R O'Meara

    Department of Molecular Genetics, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Jonathan D Plumb

    Program in Cell Biology, The Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Leah E Cowen

    Department of Molecular Genetics, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Sergio Grinstein

    Program in Cell Biology, The Hospital for Sick Children, Toronto, Canada
    For correspondence
    sergio.grinstein@sickkids.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0795-4160

Funding

Canadian Institutes of Health Research (FDN‑143202)

  • Sergio Grinstein

Natural Sciences and Engineering Research Council of Canada (462167)

  • Leah E Cowen

Canadian Institutes of Health Research (PJT-148548)

  • Leah E Cowen

Canadian Institutes of Health Research (MOP-86452)

  • Leah E Cowen

Canadian Institutes of Health Research (MOP-119520)

  • Leah E Cowen

Heart and Stroke Foundation of Canada (Heart and Stroke Pfizer Fellowship)

  • Michelle E Maxson

National Institutes of Health (AI115947-01)

  • Teresa R O'Meara

The Research Training Group 1459

  • Xenia Naj

Natural Sciences and Engineering Research Council of Canada (6261)

  • Leah E Cowen

Canadian Institutes of Health Research (FDN-154288)

  • Leah E Cowen

Canadian Institutes of Health Research (PJT-153403)

  • Leah E Cowen

National Institutes of Health (1R01AI127375-01)

  • Leah E Cowen

Natural Sciences and Engineering Research Council of Canada (477598)

  • Leah E Cowen

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Dominique Soldati-Favre, University of Geneva, Switzerland

Publication history

  1. Received: January 4, 2018
  2. Accepted: March 16, 2018
  3. Accepted Manuscript published: March 19, 2018 (version 1)
  4. Version of Record published: April 12, 2018 (version 2)

Copyright

© 2018, Maxson et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Michelle E Maxson
  2. Xenia Naj
  3. Teresa R O'Meara
  4. Jonathan D Plumb
  5. Leah E Cowen
  6. Sergio Grinstein
(2018)
Integrin-based diffusion barrier separates membrane domains enabling formation of microbiostatic frustrated phagosomes
eLife 7:e34798.
https://doi.org/10.7554/eLife.34798

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