Role of Ficolin-A and Lectin Complement Pathway in the Innate Defense against Pathogenic Aspergillus Species
Role of Ficolin-A and Lectin Complement Pathway in the Innate Defense against Pathogenic Aspergillus Species
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DOI：
10.1128/iai.00032-13
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发表时间：
2013-05-01
影响因子：
3.1
通讯作者：
Schelenz, Silke
中科院分区：
文献类型：
--
作者：
Bidula, Stefan;Kenawy, Hany;Schelenz, Silke
曲霉菌是腐生性霉菌，会在免疫受损的宿主中引起危及生命的侵袭性真菌感染。据报道，天然免疫识别，特别是调理和补体激活机制，是抵御真菌的不可或缺的一部分。结果表明，补体组分斐果林-A以浓度依赖的方式与曲霉分生孢子和菌丝结合，并被N-乙酰氨基葡萄糖和N-乙酰氨基半乳糖抑制。与烟曲霉和土曲霉的结合不依赖于钙，而与黄曲霉和黑曲霉的结合依赖于钙。在低pH条件下，菲科林-A与分生孢子的结合增加，而调理作用使分生孢子与A549呼吸道上皮细胞的结合增强。在补体激活的凝集素途径的研究中，无花果-A-调理分生孢子不会导致凝集素途径特异性的C4沉积。相反，凝集素甘露糖结合凝集素C(MBL-C)而不是MBL-A在没有无花果A的情况下能有效地激活烟曲霉凝集素途径。此外，非花青素-A的调理作用导致了促炎细胞因子白介素8的调节。我们的结论是，无花果-A可能通过调理分生孢子，通过增强对上皮细胞的黏附和调节炎症来固定真菌，从而在对抗曲霉的天然防御中发挥重要作用。然而，似乎其他免疫模式识别分子，即集合素MBL-C的分子，参与曲霉-凝集素补体途径的激活，而不是无花果-A。
Aspergillus species are saprophytic molds causing life-threatening invasive fungal infections in the immunocompromised host. Innate immune recognition, in particular, the mechanisms of opsonization and complement activation, has been reported to be an integral part of the defense against fungi. We have shown that the complement component ficolin-A significantly binds to Aspergillus conidia and hyphae in a concentration-dependent manner and was inhibited by N-acetylglucosamine and N-acetylgalactosamine. Calcium-independent binding to Aspergillus fumigatus and A. terreus was observed, but binding to A. flavus and A. niger was calcium dependent. Ficolin-A binding to conidia was increased under low-pH conditions, and opsonization led to enhanced binding of conidia to A549 airway epithelial cells. In investigations of the lectin pathway of complement activation, ficolin-A-opsonized conidia did not lead to lectin pathway-specific C4 deposition. In contrast, the collectin mannose binding lectin C (MBL-C) but not MBL-A led to efficient lectin pathway activation on A. fumigatus in the absence of ficolin-A. In addition, ficolin-A opsonization led to a modulation of the proinflammatory cytokine interleukin-8. We conclude that ficolin-A may play an important role in the innate defense against Aspergillus by opsonizing conidia, immobilizing this fungus through enhanced adherence to epithelial cells and modulation of inflammation. However, it appears that other immune pattern recognition molecules, i.e., those of the collectin MBL-C, are involved in the Aspergillus-lectin complement pathway activation rather than ficolin-A.