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

被引：210

作者：

Akoumianaki, Tonia ^{[1
]}

Kyrmizi, Irene ^{[1
,2
]}

Valsecchi, Isabel ^{[3
]}

Gresnigt, Mark S. ^{[4
,5
]}

Samonis, George ^{[1
]}

Drakos, Elias ^{[1
]}

Boumpas, Dimitrios ^{[1
,2
]}

Muszkieta, Laetitia ^{[3
]}

Prevost, Marie-Christine ^{[4
,5
]}

Kontoyiannis, Dimitrios P. ^{[6
]}

Chavakis, Triantafyllos ^{[7
]}

Netea, Mihai G. ^{[4
,5
]}

van de Veerdonk, Frank L. ^{[4
,5
]}

Brakhage, Axel A. ^{[8
,9
]}

El-Benna, Jamel ^{[10
,11
]}

Beauvais, Anne ^{[3
]}

Latge, Jean-Paul ^{[3
]}

Chamilos, Georgios ^{[1
,2
]}

机构：

[1] Univ Crete, Dept Med, Iraklion 71300, Crete, Greece

[2] Fdn Res & Technol, Inst Mol Biol & Biotechnol, Iraklion 71300, Crete, Greece

[3] Inst Pasteur, Unite Aspergillus, F-75015 Paris, France

[4] Inst Pasteur, Plateforme Microscopie Elect, F-75015 Paris, France

[5] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6500 HB Nijmegen, Netherlands

[6] Univ Texas MD Anderson Canc Ctr, Dept Infect Dis, Houston, TX 77030 USA

[7] Tech Univ Dresden, Dept Clin Pathobiochem, D-01307 Dresden, Germany

[8] Leibniz Inst Nat Product Res & Infect Biol HKI, Dept Mol & Appl Microbiol, D-07745 Jena, Germany

[9] Univ Jena, D-07745 Jena, Germany

[10] Ctr Rech Inflammat, INSERM, U1149, CNRS,ERL8252, F-75018 Paris, France

[11] Univ Paris Diderot, Sorbonne Paris Cite, Lab Excellence, F-75013 Paris, France

来源：

CELL HOST & MICROBE | 2016年 / 19卷 / 01期

关键词：

BETA-GLUCAN RECEPTOR; NADPH OXIDASE; NONCANONICAL AUTOPHAGY; IMMUNE RECOGNITION; FUMIGATUS CONIDIA; HUMAN NEUTROPHILS; MACROPHAGES; RECRUITMENT; ACTIVATION; PHAGOSOMES;

D O I：

10.1016/j.chom.2015.12.002

中图分类号：

Q93 [微生物学];

学科分类号：

071005 [微生物学];

摘要：

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.

引用

页码：79 / 90

页数：12

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