Iron restriction inside macrophages regulates pulmonary host defense against Rhizopus species
PublisherNature Publishing Group
MetadataShow full item record
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).
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85051929470&doi=10.1038%2fs41467-018-05820-2&partnerID=40&md5=e647d90d63f2f3ec03dbae9c0a83b307; http://hdl.handle.net/10713/9740
- In vivo bronchoalveolar macrophage defense against Rhizopus oryzae and Aspergillus fumigatus.
- Authors: Waldorf AR, Levitz SM, Diamond RD
- Issue date: 1984 Nov
- Pulmonary defense mechanisms against opportunistic fungal pathogens.
- Authors: Waldorf AR
- Issue date: 1989
- GRP78 and Integrins Play Different Roles in Host Cell Invasion during Mucormycosis.
- Authors: Alqarihi A, Gebremariam T, Gu Y, Swidergall M, Alkhazraji S, Soliman SSM, Bruno VM, Edwards JE Jr, Filler SG, Uppuluri P, Ibrahim AS
- Issue date: 2020 Jun 2
- Inhibition of EGFR Signaling Protects from Mucormycosis.
- Authors: Watkins TN, Gebremariam T, Swidergall M, Shetty AC, Graf KT, Alqarihi A, Alkhazraji S, Alsaadi AI, Edwards VL, Filler SG, Ibrahim AS, Bruno VM
- Issue date: 2018 Aug 14
- Mucorales Species and Macrophages.
- Authors: Nicolás FE, Murcia L, Navarro E, Navarro-Mendoza MI, Pérez-Arques C, Garre V
- Issue date: 2020 Jun 26