Aspergillus Cell Wall Melanin Blocks LC3-Associated Phagocytosis to Promote Pathogenicity
| العنوان: | Aspergillus Cell Wall Melanin Blocks LC3-Associated Phagocytosis to Promote Pathogenicity |
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| المؤلفون: | Frank L. van de Veerdonk, Elias Drakos, Triantafyllos Chavakis, Isabel Valsecchi, Dimitrios P. Kontoyiannis, Anne Beauvais, Axel A. Brakhage, Irene Kyrmizi, Tonia Akoumianaki, Marie Christine Prevost, Jean-Paul Latgé, Mark S. Gresnigt, Laetitia Muszkieta, Dimitrios T. Boumpas, Georgios Chamilos, Mihai G. Netea, Jamel El-Benna, George Samonis |
| المصدر: | Cell Host & Microbe, 19, 1, pp. 79-90 Cell Host & Microbe, 19, 79-90 |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Phagocytosis, 030106 microbiology, ATG5, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Virulence, Microbiology, Autophagy-Related Protein 5, Aspergillus fumigatus, Cell wall, Melanin, Mice, 03 medical and health sciences, Cell Wall, Phagosomes, Immunology and Microbiology(all), Virology, Animals, Aspergillosis, Humans, Molecular Biology, Phagosome, Melanins, Aspergillus, biology, biology.organism_classification, Parasitology, Microtubule-Associated Proteins |
| الوصف: | Item does not contain fulltext 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. |
| تدمد: | 1931-3128 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1c54f26f9cff99b2d64b7559fc73274fTest https://doi.org/10.1016/j.chom.2015.12.002Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1c54f26f9cff99b2d64b7559fc73274f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19313128 |
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