RRC ID 36004
Author Akoumianaki T, Kyrmizi I, Valsecchi I, Gresnigt MS, Samonis G, Drakos E, Boumpas D, Muszkieta L, Prevost MC, Kontoyiannis DP, Chavakis T, Netea MG, van de Veerdonk FL, Brakhage AA, El-Benna J, Beauvais A, Latge JP, Chamilos G.
Title Aspergillus Cell Wall Melanin Blocks LC3-Associated Phagocytosis to Promote Pathogenicity.
Journal Cell Host Microbe
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.
Volume 19(1)
Pages 79-90
Published 2016-1-13
DOI 10.1016/j.chom.2015.12.002
PII S1931-3128(15)00494-1
PMID 26749442
MeSH Animals Aspergillosis / immunology Aspergillosis / microbiology* Aspergillosis / physiopathology Aspergillus fumigatus / genetics Aspergillus fumigatus / metabolism* Aspergillus fumigatus / pathogenicity* Autophagy-Related Protein 5 Cell Wall / genetics Cell Wall / metabolism* Humans Melanins / genetics Melanins / metabolism* Mice Microtubule-Associated Proteins / genetics Microtubule-Associated Proteins / immunology* Phagocytosis* Phagosomes / immunology Virulence
IF 15.923
Times Cited 80
Mice RBRC02975