PDF(Pubmed)
Abstract：
Chromoblastomycosis is a chronic granulomatous subcutaneous fungal disease caused mainly by Fonsecaea monophora in southern China. Melanin is an important virulence factor in wild strain (Mel+), and the strains lack of the polyketide synthase gene is a melanin-deficient mutant strain (Mel-). We investigated the effect of melanin in F. monophora on Dectin-1 receptor-mediated immune responses in macrophages. Conidia and tiny hyphae of Mel+ and Mel- were co-cultured with THP-1 macrophages expressing normal or low levels of Dectin-1. Compare the killing rate, phagocytosis rate, and expression levels of the inflammatory cytokines tumour necrosis factor-α, interleukin-1β, interleukin-6, and nitric oxide in each group. The results showed that the killing rate, phagocytosis rate, and pro-inflammatory factor levels of Mel+ infected macrophages with normal expression of Dectin-1 were lower than those of Mel-. And the knockdown of Dectin-1 inhibited the phagocytic rate, killing rate, and proinflammatory factor expression in macrophages infected with Mel+ and Mel-. And there was no significant difference in the above indexes between Mel+ and Mel- groups in Dectin-1 knockdown macrophages. In summary, the study reveals that melanin of F. monophora inhibits the immune response effect of the host by hindering its binding to Dectin-1 on the surface of macrophage, which may lead to persistent fungal infections.
摘要：
染色体真菌病是中国南方一种主要由单叶毛虫引起的慢性肉芽肿性皮下真菌病。黑色素是野生菌株(Mel+)的重要毒力因子,缺乏聚酮合成酶基因的菌株是黑色素缺陷型突变菌株(Mel-)。我们研究了黑色素对巨噬细胞中Dectin-1受体介导的免疫反应的影响。将分生孢子和Mel和Mel-的微小菌丝与表达正常或低水平的Dectin-1的THP-1巨噬细胞共培养。比较杀戮率，吞噬率，和炎症细胞因子肿瘤坏死因子-α的表达水平，白细胞介素-1β，各组白细胞介素-6和一氧化氮。结果表明，杀灭率，吞噬率，Dectin-1正常表达的Mel+感染巨噬细胞的促炎因子水平低于Mel-。Dectin-1的敲除抑制了吞噬率，杀灭率,Mel+和Mel-感染的巨噬细胞中促炎因子的表达。Dectin-1敲除巨噬细胞的上述指标在Mel和Mel-组之间没有显着差异。总之,这项研究表明，F.monophora的黑色素通过阻碍其与巨噬细胞表面的Dectin-1的结合来抑制宿主的免疫反应效应，这可能导致持续的真菌感染。
