Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
Manchester Fungal Infection Group, Division of Evolution, Infection, and Genomics, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Nat Microbiol. 2024 Oct;9(10):2710-2726. doi: 10.1038/s41564-024-01782-y. Epub 2024 Aug 27.
Aspergillus fumigatus causes aspergillosis and relies on asexual spores (conidia) for initiating host infection. There is scarce information about A. fumigatus proteins involved in fungal evasion and host immunity modulation. Here we analysed the conidial surface proteome of A. fumigatus, two closely related non-pathogenic species, Aspergillus fischeri and Aspergillus oerlinghausenensis, as well as pathogenic Aspergillus lentulus, to identify such proteins. After identifying 62 proteins exclusively detected on the A. fumigatus conidial surface, we assessed null mutants for 42 genes encoding these proteins. Deletion of 33 of these genes altered susceptibility to macrophage, epithelial cells and cytokine production. Notably, a gene that encodes a putative glycosylasparaginase, modulating levels of the host proinflammatory cytokine IL-1β, is important for infection in an immunocompetent murine model of fungal disease. These results suggest that A. fumigatus conidial surface proteins are important for evasion and modulation of the immune response at the onset of fungal infection.
烟曲霉引起曲霉病,依赖无性孢子(分生孢子)引发宿主感染。关于参与真菌逃避和宿主免疫调节的烟曲霉蛋白,信息十分匮乏。在此,我们分析了烟曲霉、两种密切相关的非致病性种(构巢曲霉和嗜热曲霉)以及致病性的尖端曲霉的分生孢子表面蛋白质组,以鉴定这些蛋白质。在鉴定出仅在烟曲霉分生孢子表面检测到的 62 种蛋白质后,我们评估了缺失编码这些蛋白质的 42 个基因的突变体。这些基因中的 33 个缺失改变了对巨噬细胞、上皮细胞和细胞因子产生的敏感性。值得注意的是,编码一种糖基天冬酰胺酶的基因,该酶可调节宿主促炎细胞因子 IL-1β 的水平,对于真菌疾病的免疫功能正常的小鼠模型中的感染很重要。这些结果表明,烟曲霉分生孢子表面蛋白对于真菌感染开始时的免疫逃避和免疫调节很重要。