Reference - Detail
| RRC ID | 88295 |
|---|---|
| Author | Andrianaki AM, Kyrmizi I, Thanopoulou K, Baldin C, Drakos E, Soliman SSM, Shetty AC, McCracken C, Akoumianaki T, Stylianou K, Ioannou P, Pontikoglou C, Papadaki HA, Tzardi M, Belle V, Etienne E, Beauvais A, Samonis G, Kontoyiannis DP, Andreakos E, Bruno VM, Ibrahim AS, Chamilos G. |
| Title | Iron restriction inside macrophages regulates pulmonary host defense against Rhizopus species. |
| Journal | Nat Commun |
| Abstract |
Mucormycosis 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. |
| Volume | 9(1) |
| Pages | 3333 |
| Published | 2018-8-20 |
| DOI | 10.1038/s41467-018-05820-2 |
| PII | 10.1038/s41467-018-05820-2 |
| PMID | 30127354 |
| PMC | PMC6102248 |
| MeSH | Animals Cell Wall / metabolism Gene Expression Regulation Host-Pathogen Interactions* Iron / metabolism* Lung / microbiology* Macrophages, Alveolar / metabolism* Macrophages, Alveolar / ultrastructure Melanins / metabolism Mice, Inbred C57BL Microbial Viability Models, Biological Mucormycosis / genetics Mucormycosis / microbiology Mucormycosis / pathology Phagosomes / metabolism Phagosomes / ultrastructure Rhizopus / growth & development Rhizopus / physiology* Spores, Fungal / physiology |
| IF | 12.121 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 22 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Mice | RBRC00806 |