School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
PLoS One. 2010 Feb 17;5(2):e9036. doi: 10.1371/journal.pone.0009036.
Aspergillus fumigatus is associated with both invasive and allergic pulmonary diseases, in different hosts. The organism is inhaled as a spore, which, if not cleared from the airway, germinates into hyphal morphotypes that are responsible for tissue invasion and resultant inflammation. Hyphae secrete multiple products that function as antigens, evoking both a protective (T(H)1-T(H)17) and destructive allergic (T(H)2) immunity. How Aspergillus allergens (Asp f proteins) participate in the development of allergic sensitization is unknown.
METHODOLOGY/PRINCIPAL FINDINGS: To determine whether Asp f proteins are strictly associated with T(H)2 responses, or represent soluble hyphal products recognized by healthy hosts, human T cell responses to crude and recombinant products were characterized by ELISPOT. While responses (number of spots producing IFN-gamma, IL-4 or IL-17) to crude hyphal antigen preparations were weak, responses to recombinant Asp f proteins were higher. Recombinant allergens stimulated cells to produce IFN-gamma more so than IL-4 or IL-17. Volunteers exhibited a diverse CD4+ and CD8+ T cell antigen recognition profile, with prominent CD4 T(H)1-responses to Asp f3 (a putative peroxismal membrane protein), Asp f9/16 (cell wall glucanase), Asp f11 (cyclophilin type peptidyl-prolyl isomerase) and Asp f22 (enolase). Strong IFN-gamma responses were reproduced in most subjects tested over 6 month intervals.
Products secreted after conidial germination into hyphae are differentially recognized by protective T cells in healthy, non-atopic individuals. Defining the specificity of the human T cell repertoire, and identifying factors that govern early responses may allow for development of novel diagnostics and therapeutics for both invasive and allergic Aspergillus diseases.
烟曲霉与不同宿主的侵袭性和过敏性肺部疾病有关。该生物作为孢子被吸入，如果不从气道中清除，就会发芽成菌丝形态，导致组织侵袭和炎症。菌丝分泌多种作为抗原的产物，引发保护性（T(H)1-T(H)17）和破坏性过敏（T(H)2）免疫。曲霉过敏原（Asp f 蛋白）如何参与过敏致敏的发展尚不清楚。
方法/主要发现：为了确定 Asp f 蛋白是否与 T(H)2 反应严格相关，还是代表健康宿主识别的可溶性菌丝产物，通过 ELISPOT 对粗提物和重组产物的人类 T 细胞反应进行了特征描述。虽然对粗提物菌丝抗原制剂的反应（产生 IFN-γ、IL-4 或 IL-17 的斑点数）较弱，但对重组 Asp f 蛋白的反应更高。重组过敏原刺激细胞产生 IFN-γ的能力强于 IL-4 或 IL-17。志愿者表现出多样化的 CD4+和 CD8+T 细胞抗原识别谱，对 Asp f3（一种假定的过氧化物酶体膜蛋白）、Asp f9/16（细胞壁葡聚糖酶）、Asp f11（亲环素型肽脯氨酰顺反异构酶）和 Asp f22（烯醇酶）表现出明显的 CD4 T(H)1 反应。在大多数测试对象中，在 6 个月的间隔内重复产生强烈的 IFN-γ反应。
在健康的非过敏个体中，分生孢子发芽成菌丝后分泌的产物被保护性 T 细胞差异识别。定义人类 T 细胞库的特异性，并确定控制早期反应的因素，可能为侵袭性和过敏性曲霉病的新型诊断和治疗方法的发展提供依据。
