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Updated: Mar 27, 2026
Live-cell Video Microscopy of Fungal Pathogen Phagocytosis
Published on: January 9, 2013
Aspergillus Cell Wall Melanin Blocks LC3-Associated Phagocytosis to Promote Pathogenicity
Tonia Akoumianaki1, Irene Kyrmizi2, Isabel Valsecchi3
1Department of Medicine, University of Crete, Foundation for Research and Technology, 71300 Heraklion, Crete, Greece.
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.
Insights
Fungal melanin conceals immune signals, preventing LC3-associated phagocytosis (LAP) and fungal killing. Melanin removal during germination is essential for activating this immune response against Aspergillus fumigatus.
Area of Science:
- Immunology
- Mycology
- Cell Biology
Background:
- Fungi evade immune detection by hiding pathogen-associated molecular patterns (PAMPs).
- Germination exposes fungal PAMPs, making them vulnerable to immune responses like LC3-associated phagocytosis (LAP).
- Aspergillus fumigatus utilizes cell wall melanin to conceal PAMPs.
Purpose of the Study:
- To investigate the role of melanin in immune evasion during fungal germination.
- To elucidate the mechanism by which melanin affects LAP activation.
- To determine the impact of melanin on the virulence of Aspergillus fumigatus.
Main Methods:
- Assessing LAP activation in wild-type and melanin-deficient Aspergillus fumigatus.
- Utilizing Atg5-deficient macrophages and mice to study the role of LAP in vivo.
- Investigating the interaction of melanin with phagosomal components, including p22phox.
Main Results:
- LAP activation during Aspergillus fumigatus germination requires the removal of cell wall melanin.
- Melanin-deficient fungi exhibit attenuated virulence, which is restored in Atg5-deficient immune cells.
- Aspergillus melanin inhibits NADPH oxidase-dependent LAP by preventing p22phox recruitment to the phagosome.
- Melanin pigments broadly block LAP activation.
Conclusions:
- Fungal melanin is a key virulence factor that actively inhibits the host immune response.
- The removal of melanin during germination is a critical step for initiating PAMP recognition and subsequent fungal killing.
- Targeting melanin-mediated immune suppression could represent a novel therapeutic strategy against fungal infections.
