論文 - 詳細
| RRC ID | 88295 |
|---|---|
| 著者 | 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. |
| タイトル | Iron restriction inside macrophages regulates pulmonary host defense against Rhizopus species. |
| ジャーナル | 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. |
| 巻・号 | 9(1) |
| ページ | 3333 |
| 公開日 | 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 22 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC00806 |