Iron restriction inside macrophages regulates pulmonary host defense against Rhizopus species.
Iron restriction inside macrophages regulates pulmonary host defense against Rhizopus species.
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DOI：
10.1038/s41467-018-05820-2
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发表时间：
2018-08-20
影响因子：
16.6
通讯作者：
Chamilos G
中科院分区：
文献类型：
--
作者：
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
毛霉菌病是一种威胁生命的呼吸道真菌感染，主要由根霉属引起。毛霉菌病的发病机制还不完全清楚，特别是铁代谢异常如何损害免疫反应。在这里，我们展示了如何，而不是其他丝状真菌，根霉属。在肺泡巨噬细胞（AM）内建立细胞内持久性。从机制上讲，缺乏根霉分生孢子的细胞内肿胀导致黑色素的表面保留，这通过抑制LC 3相关的吞噬作用诱导吞噬体成熟停滞。根霉的细胞内抑制是一个重要的效应机制，因为免疫活性小鼠感染肿胀的分生孢子，逃避吞噬，导致急性致死。一致地，AM耗竭显著增加毛霉菌病的易感性。宿主和病原体转录组学、铁补充研究和真菌途径铁同化的遗传操作表明，巨噬细胞内的铁限制调节对根霉的免疫。我们的研究结果揭示了毛霉菌病的发病机制，并揭示了巨噬细胞介导的营养免疫对丝状真菌的作用。毛霉菌病是一种威胁生命的呼吸道真菌感染，通常发生在铁代谢异常的患者中。在这里，作者表明，铁限制在吞噬体的巨噬细胞是一个重要组成部分的宿主防御根霉，主要物种引起毛霉病。
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. Mucormycosis is a life-threatening respiratory fungal infection that typically occurs in patients with abnormalities in iron metabolism. Here the authors show that iron restriction inside the phagosome of macrophages is an essential component of the host defense against Rhizopus, the main species causing mucormycosis.
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影响因子：
6.4
作者：
Kontoyiannis, DP;Lionakis, MS;Raad, II
通讯作者：
Raad, II
影响因子：
15.9
作者：
Bedoret, Denis;Wallemacq, Hugues;Bureau, Fabrice
通讯作者：
Bureau, Fabrice
影响因子：
30.3
作者：
Akoumianaki, Tonia;Kyrmizi, Irene;Chamilos, Georgios
通讯作者：
Chamilos, Georgios
DOI：
10.1073/pnas.242614699
发表时间：
2002-11-26
影响因子：
11.1
作者：
Drakesmith, H;Sweetland, E;Townsend, ARM
通讯作者：
Townsend, ARM
影响因子：
8.8
作者：
FAVA, F;DI GIOIA, D;MARCHETTI, L
通讯作者：
MARCHETTI, L