Phagocytosis of Aspergillus fumigatus conidia by murine macrophages involves recognition by the dectin-1 beta-glucan receptor and Toll-like receptor 2
Phagocytosis of Aspergillus fumigatus conidia by murine macrophages involves recognition by the dectin-1 beta-glucan receptor and Toll-like receptor 2
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DOI：
10.1111/j.1462-5822.2006.00796.x
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发表时间：
2007-02-01
影响因子：
3.4
通讯作者：
Ebel, Frank
中科院分区：
文献类型：
--
作者：
Luther, Kathrin;Torosantucci, Antonella;Ebel, Frank
烟曲霉是一种引起免疫功能低下患者严重感染的真菌病原体。为了清除吸入的分生孢子，需要先天免疫系统的有效反应。巨噬细胞代表了第一道防线，吞噬和杀死分生孢子。c型凝集素代表一个受体家族，可识别病原体特异性碳水化合物。其中之一是β - 1-3葡聚糖，它是真菌细胞壁的主要成分。本研究证明β - 1-3葡聚糖在烟曲霉分生孢子的消灭中起重要作用。Laminarin是一种可溶性β - 1-3葡聚糖和dectin-1的抗体，dectin-1是一种众所周知的β - 1-3葡聚糖受体，可显著抑制分生孢子吞噬。在静止的分生孢子中检测到少量的表面可接近的β - 1-3葡聚糖，而在萌发和感染早期出现的小孢子以及pksP突变株的静止分生孢子中检测到大量的表面可接近的β - 1-3葡聚糖。肿胀的分生孢子也显示大量的β - 1-3葡聚糖，尽管呈不规则斑点状。静止的pksP突变型分生孢子和肿胀的野生型分生孢子被高效吞噬，从而证实了β - 1-3葡聚糖与分生孢子吞噬的相关性。此外，我们发现TLR2和接头蛋白MyD88是有效的分生孢子吞噬所必需的，这表明TLR2介导的烟状芽孢杆菌的识别与吞噬反应之间存在联系。
Aspergillus fumigatus is a fungal pathogen causing severe infections in immunocompromised patients. For clearance of inhaled conidia, an efficient response of the innate immune system is required. Macrophages represent the first line of defence and ingest and kill conidia. C-type lectins represent a family of receptors, which recognize pathogen-specific carbohydrates. One of them is beta 1-3 glucan, a major component of the fungal cell wall. Here we provide evidence that beta 1-3 glucan plays an important role for the elimination of A. fumigatus conidia. Laminarin, a soluble beta 1-3 glucan and antibodies to dectin-1, a well known beta 1-3 glucan receptor, significantly inhibited conidial phagocytosis. On resting conidia low amounts of surface accessible beta 1-3 glucan were detected, whereas high amounts were found on small spores that appear early during germination and infection as well as on resting conidia of a pksP mutant strain. Swollen conidia also display larger quantities of beta 1-3 glucan, although in an irregular spotted pattern. Resting pksP mutant conidia and swollen wild-type conidia are phagocytosed with high efficiency thereby confirming the relevance of beta 1-3 glucans for conidial phagocytosis. Additionally we found that TLR2 and the adaptor protein MyD88 are required for efficient conidial phagocytosis, suggesting a link between the TLR2-mediated recognition of A. fumigatus and the phagocytic response.