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Cell Host Microbe. 2016 Jan 13;19(1):79-90. doi: 10.1016/j.chom.2015.12.002. Epub 2015 Dec 31.

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

Author information

1
Department of Medicine, University of Crete, Foundation for Research and Technology, 71300 Heraklion, Crete, Greece.
2
Department of Medicine, University of Crete, Foundation for Research and Technology, 71300 Heraklion, Crete, Greece; Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, 71300 Heraklion, Crete, Greece.
3
Unité des Aspergillus, Institut Pasteur, Paris 75015, France.
4
Plateforme de Microscopie Electronique, Institut Pasteur, Paris 75015, France; Department of Internal Medicine, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands.
5
Department of Infectious Diseases, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA.
6
Department of Clinical Pathobiochemistry, Technische Universität Dresden, 01307 Dresden, Germany.
7
Department of Molecular and Applied Microbiology, Leibniz-Institute for Natural Product Research and Infection Biology (HKI) and Friedrich Schiller University, 07745 Jena, Germany.
8
Inserm, U1149, CNRS-ERL8252, Centre de Recherche sur l'Inflammation, 75018 Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d'Excellence, 75013 Paris, France.
9
Unité des Aspergillus, Institut Pasteur, Paris 75015, France. Electronic address: jean-paul.latge@pasteur.fr.
10
Department of Medicine, University of Crete, Foundation for Research and Technology, 71300 Heraklion, Crete, Greece; Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, 71300 Heraklion, Crete, Greece. Electronic address: hamilos@imbb.forth.gr.

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.

PMID:
26749442
DOI:
10.1016/j.chom.2015.12.002
[Indexed for MEDLINE]
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