Browsing by Author "Neves, Nuno M."
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- Calcium sequestration by fungal melanin inhibits calcium–calmodulin signalling to prevent LC3-associated phagocytosisPublication . Kyrmizi, Irene; Ferreira, Helena; Carvalho, Agostinho; Figueroa, Julio Alberto Landero; Zarmpas, Pavlos; Cunha, Cristina; Akoumianaki, Tonia; Stylianou, Kostas; Deepe, George S.; Samonis, George; Lacerda, João; Campos, António; Kontoyiannis, Dimitrios P.; Mihalopoulos, Nikolaos; Kwon-Chung, Kyung J.; El-Benna, Jamel; Valsecchi, Isabel; Beauvais, Anne; Brakhage, Axel A.; Neves, Nuno M.; Latge, Jean-Paul; Chamilos, GeorgiosLC3-associated phagocytosis (LAP) is a non-canonical autophagy pathway regulated by Rubicon, with an emerging role in immune homeostasis and antifungal host defence. Aspergillus cell wall melanin protects conidia (spores) from killing by phagocytes and promotes pathogenicity through blocking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent activation of LAP. However, the signalling regulating LAP upstream of Rubicon and the mechanism of melanin-induced inhibition of this pathway remain incompletely understood. Herein, we identify a Ca2+ signalling pathway that depends on intracellular Ca2+ sources from endoplasmic reticulum, endoplasmic reticulum-phagosome communication, Ca2+ release from phagosome lumen and calmodulin (CaM) recruitment, as a master regulator of Rubicon, the phagocyte NADPH oxidase NOX2 and other molecular components of LAP. Furthermore, we provide genetic evidence for the physiological importance of Ca2+-CaM signalling in aspergillosis. Finally, we demonstrate that Ca2+ sequestration by Aspergillus melanin inside the phagosome abrogates activation of Ca2+-CaM signalling to inhibit LAP. These findings reveal the important role of Ca2+-CaM signalling in antifungal immunity and identify an immunological function of Ca2+ binding by melanin pigments with broad physiological implications beyond fungal disease pathogenesis.
- Complete Specification of APIs and Protocols for the MAFTIA MiddlewarePublication . Armstrong, J.; Cachin, C.; Correia, Miguel; Costa, A.; Miranda, Hugo; Neves, Nuno Ferreira; Neves, Nuno M.; Poritz, J. A.; Randell, B.; Lung, Lau Cheuk; Rodrigues, Luís; Stroud, Robert J.; Veríssimo, Paulo; Waidner, M.; Welch, I. S.This document describes the complete specification of the APIs and Protocols for the MAFTIA Middleware. The architecture of the middleware subsystem has been described in a previous document, where the several modules and services were introduced: Activity Services; Communication Services; Network Abstraction; Trusted and Untrusted Components. The purpose of the present document is to make concrete the functionality of the middleware components, by defining their application programming interfaces, and describing the protocols implementing the above-mentioned functionality
- First Specification of APIs and Protocols for the MAFTIA MiddlewarePublication . Armstrong, J.; Cachin, C.; Correia, Miguel; Costa, A.; Miranda, Hugo; Neves, Nuno Ferreira; Neves, Nuno M.; Poritz, J. A.; Randell, B.; Lung, Lau Cheuk; Rodrigues, Luís; Stroud, Robert J.; Veríssimo, Paulo; Waidner, M.; Welch, I. S.This document describes the first specification of the APIs and Protocols for the MAFTIA Middleware. The architecture of the middleware subsystem has been described in a previous document, where the several modules and services were introduced: Activity Services; Communication Services; Network Abstraction; Trusted and Untrusted Components. The purpose of the present document is to make concrete the functionality of the middleware components, by defining their application programming interfaces, and describing the protocols implementing the above-mentioned functionality