Melanin from Fonsecaea pedrosoi induces production of human antifungal antibodies and enhances the antimicrobial efficacy of phagocytes
Melanin from Fonsecaea pedrosoi induces production of human antifungal antibodies and enhances the antimicrobial efficacy of phagocytes
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DOI：
10.1128/iai.72.1.229-237.2004
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发表时间：
2004-01-01
影响因子：
3.1
通讯作者：
Rodrigues, ML
中科院分区：
文献类型：
--
作者：
Alviano, DS;Franzen, AJ;Rodrigues, ML
黄斑病菌是一种产生黑色素的真菌病原体。黑素的功能及其在蜱虫感染时的保护性免疫反应中的可能影响尚不清楚。在这项工作中，用蛋白酶和糖苷酶处理后，再用变性剂和热浓酸处理后，木霉菌丝体留下黑色残留物。扫描电镜显示，这种经过处理的黑化残留物在形状和大小上与完整菌丝非常相似。从孢子菌分生孢子或硬化型孢子的培养液中也分离到黑色素颗粒。分泌的黑色素与受感染的人类患者的血清有反应，表明F. pedrosoi在体内合成黑色素。从患者血清中纯化抗黑色素抗体，采用间接免疫荧光法进行分析。它们与来自患者病变的硬化细胞以及体外培养的硬化体、分生孢子、菌丝和消化的残留物发生反应。用纯化的抗黑色素抗体处理黑曲霉可抑制其体外生长。在有黑色素存在的情况下，木褐梭菌与吞噬细胞的相互作用导致宿主细胞更高水平的真菌内化和破坏，并伴有更大程度的氧化破裂。综上所述，这些结果表明，黑素是一种具有免疫活性的真菌结构，可以激活体液和细胞反应，从而帮助宿主防御控制嗜色菌病。
Fonsecaea pedrosoi is a fungal pathogen that produces melanin. The functions of melanin and its possible influence in the protective immunological response during infection by F. pedrosoi are not known. In this work, treatment of F. pedrosoi mycelia with proteases and glycosidases followed by a denaturing agent and hot concentrated acid left a black residue. Scanning electron microscopy demonstrated that this processed melanized residue resembled very closely the intact mycelium in shape and size. Melanin particles were also isolated from culture fluids of conidia or sclerotic forms of F. pedrosoi. Secreted melanins were reactive with sera from infected human patients, suggesting that F. pedrosoi synthesizes melanin in vivo. The antibodies against melanin were purified from patients' sera and analyzed by indirect immunofluorescence. They reacted with sclerotic cells from patients' lesions as well as with sclerotic bodies cultivated in vitro, conidia, mycelia, and digested residues. Treatment of F. pedrosoi with purified antibodies against melanin inhibited fungal growth in vitro. The interaction of F. pedrosoi with phagocytes in the presence of melanin resulted in higher levels of fungal internalization and destruction by host cells, which was accompanied by greater degrees of oxidative burst. Taken together, these results indicate that melanin from F. pedrosoi is an immunologically active fungal structure that activates humoral and cellular responses that could help the control of chromoblastomycosis by host defenses.