Aspergillus fumigatus triggers inflammatory responses by stage-specific beta-glucan display.
Aspergillus fumigatus triggers inflammatory responses by stage-specific beta-glucan display.
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DOI：
10.1371/journal.ppat.0010030
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发表时间：
2005-11
期刊：
影响因子：
6.7
通讯作者：
Pamer EG
中科院分区：
文献类型：
--
作者：
Hohl TM;Van Epps HL;Rivera A;Morgan LA;Chen PL;Feldmesser M;Pamer EG
真菌孢子（分生孢子）的吸入通常发生，在特定情况下，可导致侵入性疾病。我们研究了小鼠对烟曲霉分生孢子的炎症反应，烟曲霉是免疫功能低下宿主中最常见的侵袭性霉菌。与休眠孢子相反，萌发的分生孢子诱导中性粒细胞募集到气道，并通过肺泡巨噬细胞分泌TNF-α/MIP-2。真菌β-葡聚糖通过其在萌发的分生孢子表面上的时间依赖性暴露而充当诱导这些炎症反应的触发剂。Dectin-1是一种识别真菌β-葡聚糖的先天性免疫受体，在体内被招募到肺泡巨噬细胞吞噬体中，肺泡巨噬细胞吞噬体具有内化的具有暴露的β-葡聚糖的分生孢子。抗体介导的Dectin-1阻断部分抑制代谢活性分生孢子对TNF-α/MIP-2的诱导。TLR-2和MyD 88介导的信号通过萌发的分生孢子对巨噬细胞活化提供了附加贡献。对萌发的分生孢子的选择性反应为先天免疫系统提供了一种机制，以限制对代谢活性的、潜在的侵入性真菌孢子的炎症反应。 烟曲霉菌是一种霉菌，形成孢子，经常被哺乳动物吸入。免疫系统正常的人吸入几百个A。烟曲霉孢子每天没有发展可检测的疾病。另一方面，免疫功能低下的宿主可以发展为侵袭性A。烟曲霉感染在这些情况下，吸入的孢子发芽并形成组织侵入性菌丝，侵入血管并传播到远端组织。本研究的目的是探讨小鼠肺部对吸入孢子的正常炎症反应。研究人员发现，孢子萌发的最早阶段，被称为“肿胀”，触发了炎症细胞进入肺气道的招募。与这一发现相一致的是，用肿胀的孢子刺激的肺源性细胞分泌了大量的蛋白质，这些蛋白质吸引炎症细胞。孢子分析显示，膨胀伴随着β-葡聚糖聚合物的表面表达。这些不存在于哺乳动物细胞表面的碳水化合物通过哺乳动物Dectin-1受体诱导信号传导，并激活促进炎症反应的基因的表达。结果表明，哺乳动物的肺已经进化出一种机制，可以区分肿胀和潜在威胁的孢子与无害的休眠孢子。
Inhalation of fungal spores (conidia) occurs commonly and, in specific circumstances, can result in invasive disease. We investigated the murine inflammatory response to conidia of Aspergillus fumigatus, the most common invasive mold in immunocompromised hosts. In contrast to dormant spores, germinating conidia induce neutrophil recruitment to the airways and TNF-α/MIP-2 secretion by alveolar macrophages. Fungal β-glucans act as a trigger for the induction of these inflammatory responses through their time-dependent exposure on the surface of germinating conidia. Dectin-1, an innate immune receptor that recognizes fungal β-glucans, is recruited in vivo to alveolar macrophage phagosomes that have internalized conidia with exposed β-glucans. Antibody-mediated blockade of Dectin-1 partially inhibits TNF-α/MIP-2 induction by metabolically active conidia. TLR-2- and MyD88-mediated signals provide an additive contribution to macrophage activation by germinating conidia. Selective responsiveness to germinating conidia provides the innate immune system with a mechanism to restrict inflammatory responses to metabolically active, potentially invasive fungal spores. Aspergillus fumigatus is a mold that forms spores that are often inhaled by mammals. Humans with normal immune systems inhale several hundred A. fumigatus spores per day without developing detectable disease. Immunocompromised hosts, on the other hand, can develop invasive A. fumigatus infections. In these cases, inhaled spores germinate and form tissue-invasive hyphae that invade blood vessels and disseminate to remote tissues. The aim of this study was to investigate the normal inflammatory response to inhaled spores in mouse lungs. The researchers found that the earliest stage of spore germination, referred to as “swelling,” triggered the recruitment of inflammatory cells into the lung airways. Consistent with this finding, lung-derived cells stimulated with swollen spores secreted copious amounts of proteins that attract inflammatory cells. Analysis of spores revealed that swelling is accompanied by surface expression of β-glucan polymers. These carbohydrates, which are not present on the surface of mammalian cells, induce signaling by the mammalian Dectin-1 receptor and activate the expression of genes that promote the inflammatory response. The results suggest that mammalian lungs have evolved a mechanism to distinguish swollen and potentially threatening spores from innocuous, dormant spores.
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Dectin-1介导β-葡聚糖的生物学作用。
DOI：
10.1084/jem.20021890
发表时间：
2003-05-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Brown GD;Herre J;Williams DL;Willment JA;Marshall AS;Gordon S
通讯作者：
Gordon S
影响因子：
3.1
作者：
Brieland, JK;Jackson, C;O'Garra, A
通讯作者：
O'Garra, A
影响因子：
3.1
作者：
Ibrahim-Granet, O;Philippe, B;Latgé, JP
通讯作者：
Latgé, JP
影响因子：
4.4
作者：
Bellocchio, S;Montagnoli, C;Romani, L
通讯作者：
Romani, L
影响因子：
20.3
作者：
Herre, J;Marshall, ASJ;Brown, GD
通讯作者：
Brown, GD