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

作者：Akoumianaki Tonia; Kyrmizi Irene; Valsecchi Isabel; Gresnigt Mark S; Samonis George; Drakos Elias; Boumpas Dimitrios; Muszkieta Laetitia; Prevost Marie Christine; Kontoyiannis Dimitrios P; Chavakis Triantafyllos; Netea Mihai G; van de Veerdonk Frank L; Brakhage Axel A; El Benna Jamel; Beauvais Anne; Latge Jean Paul^*; Chamilos Georgios^*

来源：Cell Host & Microbe, 2016, 19(1): 79-90.

DOI：10.1016/j.chom.2015.12.002

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, beta-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.

• 出版日期2016-1-13