| Literature DB >> 26749442 |
Tonia Akoumianaki1, Irene Kyrmizi2, Isabel Valsecchi3, Mark S Gresnigt4, George Samonis1, Elias Drakos1, Dimitrios Boumpas2, Laetitia Muszkieta3, Marie-Christine Prevost4, Dimitrios P Kontoyiannis5, Triantafyllos Chavakis6, Mihai G Netea4, Frank L van de Veerdonk4, Axel A Brakhage7, Jamel El-Benna8, Anne Beauvais3, Jean-Paul Latge9, Georgios Chamilos10.
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.Entities:
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Year: 2015 PMID： 26749442 DOI： 10.1016/j.chom.2015.12.002
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023