Aspergillus Cell Wall Melanin Blocks LC3-Associated Phagocytosis to Promote Pathogenicity

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Tonia Akoumianaki - , University of Crete (Author)
  • Irene Kyrmizi - , University of Crete, Foundation for Research and Technology-Hellas (Author)
  • Isabel Valsecchi - , Institut Pasteur Paris (Author)
  • Mark S. Gresnigt - , Institut Pasteur Paris, Radboud University Nijmegen (Author)
  • George Samonis - , University of Crete (Author)
  • Elias Drakos - , University of Crete (Author)
  • Dimitrios Boumpas - , University of Crete, Foundation for Research and Technology-Hellas (Author)
  • Laetitia Muszkieta - , Institut Pasteur Paris (Author)
  • Marie Christine Prevost - , Institut Pasteur Paris, Radboud University Nijmegen (Author)
  • Dimitrios P. Kontoyiannis - , University of Texas Health Science Center at Houston (Author)
  • Triantafyllos Chavakis - , Institute of Clinical Chemistry and Laboratory Medicine (Author)
  • Mihai G. Netea - , Institut Pasteur Paris, Radboud University Nijmegen (Author)
  • Frank L. Van De Veerdonk - , Institut Pasteur Paris, Radboud University Nijmegen (Author)
  • Axel A. Brakhage - , Friedrich Schiller University Jena (Author)
  • Jamel El-Benna - , Centre de Recherche sur l'Inflammation, Université Paris Cité (Author)
  • Anne Beauvais - , Institut Pasteur Paris (Author)
  • Jean Paul Latge - , Institut Pasteur Paris (Author)
  • Georgios Chamilos - , University of Crete, Foundation for Research and Technology-Hellas (Author)

Abstract

Concealing pathogen-associated molecular patterns (PAMPs) is a principal strategy used by fungi to avoid immune recognition. Surface exposure of PAMPs during germination can leave the pathogen vulnerable. Accordingly, β-glucan surface exposure during Aspergillus fumigatus germination activates an Atg5-dependent autophagy pathway termed LC3-associated phagocytosis (LAP), which promotes fungal killing. We found that LAP activation also requires the genetic, biochemical or biological (germination) removal of A. fumigatus cell wall melanin. The attenuated virulence of melanin-deficient A. fumigatus is restored in Atg5-deficient macrophages and in mice upon conditional inactivation of Atg5 in hematopoietic cells. Mechanistically, Aspergillus melanin inhibits NADPH oxidase-dependent activation of LAP by excluding the p22phox subunit from the phagosome. Thus, two events that occur concomitantly during germination of airborne fungi, surface exposure of PAMPs and melanin removal, are necessary for LAP activation and fungal killing. LAP blockade is a general property of melanin pigments, a finding with broad physiological implications.

Details

Original languageEnglish
Pages (from-to)79-90
Number of pages12
JournalCell Host and Microbe
Volume19
Issue number1
Publication statusPublished - 13 Jan 2016
Peer-reviewedYes

External IDs

researchoutputwizard legacy.publication#72203
Scopus 84959477976
PubMed 26749442

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