GSTDTAP  > 资源环境科学
DOI10.1038/s41467-018-07537-8
Iron restriction inside macrophages regulates pulmonary host defense against Rhizopus species
Andrianaki, Angeliki M.1; Kyrmizi, Irene1,2; Thanopoulou, Kalliopi3; Baldin, Clara4; Drakos, Elias1; Soliman, Sameh S. M.5; Shetty, Amol C.6; McCracken, Carrie6; Akoumianaki, Tonia1; Stylianou, Kostas1; Ioannou, Petros1; Pontikoglou, Charalampos1; Papadaki, Helen A.1; Tzardi, Maria1; Belle, Valerie7; Ettiene, Emilien7; Beauvais, Anne8; Samonis, George1; Kontoyiannis, Dimitrios P.9; Andreakos, Evangelos3; Bruno, Vincent M.6; Ibrahim, Ashraf S.4,10; Chamilos, Georgios1,2
2018-08-20
发表期刊NATURE COMMUNICATIONS
ISSN2041-1723
出版年2018
卷号9
文章类型Article
语种英语
国家Greece; USA; U Arab Emirates; France
英文摘要

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.


领域资源环境
收录类别SCI-E
WOS记录号WOS:000442123600008
WOS关键词SURVEILLANCE NETWORK TRANSNET ; INVASIVE FUNGAL-INFECTIONS ; ASPERGILLUS-FUMIGATUS ; IN-VITRO ; TRANSPLANT RECIPIENTS ; CELL-WALL ; MUCORMYCOSIS ; ZYGOMYCOSIS ; ORYZAE ; MELANIN
WOS类目Multidisciplinary Sciences
WOS研究方向Science & Technology - Other Topics
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被引频次:87[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://119.78.100.173/C666/handle/2XK7JSWQ/204110
专题资源环境科学
作者单位1.Univ Crete, Fdn Res & Technol, Dept Med, Iraklion 71300, Crete, Greece;
2.Fdn Res & Technol, Inst Mol Biol & Biotechnol, Iraklion 71300, Crete, Greece;
3.Acad Athens, Biomed Res Fdn, Ctr Clin Expt Surg & Translat Res, Lab Immunobiol, Athens 11527, Greece;
4.Harbor Univ Calif Angeles UCLA Med Ctr, Los Angeles Biomed Res Inst, Div Infect Dis, St Johns Cardiovasc Res Ctr, 1124 West Carson St, Torrance, CA 90502 USA;
5.Univ Sharjah, Coll Pharm, Sharjah Inst Med Res, POB 27272, Sharjah, U Arab Emirates;
6.Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA;
7.Aix Marseille Univ, CNRS, BIP UMR 7281, IMM FR 3479, 31 Chemin J Aiguier, F-13402 Marseille, France;
8.Inst Pasteur, Unite Aspergillus, F-75015 Paris, France;
9.Univ Texas MD Anderson Canc Ctr, Dept Infect Dis Infect Control & Employee Hlth, Houston, TX 77030 USA;
10.UCLA, David Geffen Sch Med, Los Angeles, CA 90095 USA
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Andrianaki, Angeliki M.,Kyrmizi, Irene,Thanopoulou, Kalliopi,et al. Iron restriction inside macrophages regulates pulmonary host defense against Rhizopus species[J]. NATURE COMMUNICATIONS,2018,9.
APA Andrianaki, Angeliki M..,Kyrmizi, Irene.,Thanopoulou, Kalliopi.,Baldin, Clara.,Drakos, Elias.,...&Chamilos, Georgios.(2018).Iron restriction inside macrophages regulates pulmonary host defense against Rhizopus species.NATURE COMMUNICATIONS,9.
MLA Andrianaki, Angeliki M.,et al."Iron restriction inside macrophages regulates pulmonary host defense against Rhizopus species".NATURE COMMUNICATIONS 9(2018).
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