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dc.contributor.authorAndrianaki, A.M.
dc.contributor.authorKyrmizi, I.
dc.contributor.authorThanopoulou, K.
dc.date.accessioned2019-06-21T18:46:30Z
dc.date.available2019-06-21T18:46:30Z
dc.date.issued2018
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85051929470&doi=10.1038%2fs41467-018-05820-2&partnerID=40&md5=e647d90d63f2f3ec03dbae9c0a83b307
dc.identifier.urihttp://hdl.handle.net/10713/9740
dc.description.abstractMucormycosis is a life-threatening respiratory fungal infection predominantly caused by Rhizopus species. Mucormycosis has incompletely understood pathogenesis, particularly how abnormalities in iron metabolism compromise immune responses. Here we show how, as opposed to other filamentous fungi, Rhizopus spp. establish intracellular persistence inside alveolar macrophages (AMs). Mechanistically, lack of intracellular swelling of Rhizopus conidia results in surface retention of melanin, which induces phagosome maturation arrest through inhibition of LC3-associated phagocytosis. Intracellular inhibition of Rhizopus is an important effector mechanism, as infection of immunocompetent mice with swollen conidia, which evade phagocytosis, results in acute lethality. Concordantly, AM depletion markedly increases susceptibility to mucormycosis. Host and pathogen transcriptomics, iron supplementation studies, and genetic manipulation of iron assimilation of fungal pathways demonstrate that iron restriction inside macrophages regulates immunity against Rhizopus. Our findings shed light on the pathogenetic mechanisms of mucormycosis and reveal the role of macrophage-mediated nutritional immunity against filamentous fungi. Copyright 2018, The Author(s).en_US
dc.description.urihttps://dx.doi.org/10.1038/s41467-018-05820-2en_US
dc.language.isoen-USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofNature Communications
dc.subject.meshMucormycosisen_US
dc.subject.meshRhizopusen_US
dc.subject.meshIronen_US
dc.subject.meshMacrophagesen_US
dc.titleIron restriction inside macrophages regulates pulmonary host defense against Rhizopus speciesen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41467-018-05820-2
dc.identifier.pmid30127354


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