Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
Department of Otorhinolaryngology - Head and Neck Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
Rhinology. 2016 Mar;54(1):51-5. doi: 10.4193/Rhino14.278.
Whilst the exact cause of chronic rhinosinusitis (CRS) remains elusive, it is clear that both inflammation and remodelling are key disease processes. Environmental fungi have been linked to airway inflammation in CRS; however, their role in the pathogenesis of this condition remains controversial. The current consensus suggests that whilst fungi may not be directly causative, it is likely that CRS patients have deficits in their innate and potentially acquired immunity, which in turn may modify their ability to react to fungi. This study used a nasal polyp explant tissue stimulation model to study the inflammatory and remodelling responses related to challenge with common airborne fungal species.
Ex vivo nasal polyp tissue from six well phenotyped CRSwNP patients undergoing functional endoscopic sinus surgery was stimulated with 1, 10 and 100 μg/ml of Alternaria alternata, Aspergillus niger, Cladosporium sphaerospermum and Penicillium notatum and compared with unchallenged polyp tissue as control. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of pro-inflammatory cytokines interleukin-6 (IL-6), granulocyte macrophage colony stimulating factor (GM-CSF) and tumour necrosis factor-α (TNF-α); and pro-remodelling cytokines transforming growth factor-b1 (TGF-b1), and basic fibroblast growth factor (bFGF) in the polyp supernatant.
Aspergillus niger stimulation increased pro-inflammatory cytokines TNF-α, GM-CSF and IL-6 whilst having little effect on the remodelling cytokines bFGF and TGF-b1. In contrast, stimulation with Cladosporium sphaerospermum, Alternaria alternata and Penicillium notatum reduced pro-inflammatory cytokines TNF-α and IL-6, but induced a dose-dependent increase in remodelling cytokines TGF-b1 and bFGF.
This study shows that common airborne fungi induce species-specific effects on the upper airway inflammatory and remodelling responses. These findings provide further immunological evidence of a disease-modifying role for fungi in CRS.
尽管慢性鼻-鼻窦炎（CRS）的确切病因仍不清楚，但很明显，炎症和重塑都是关键的疾病过程。环境真菌与 CRS 中的气道炎症有关；然而，它们在这种疾病发病机制中的作用仍存在争议。目前的共识认为，尽管真菌可能不是直接致病因素，但 CRS 患者的先天免疫和潜在获得性免疫可能存在缺陷，这反过来可能会改变他们对真菌的反应能力。本研究使用鼻息肉组织刺激模型研究了与常见空气传播真菌物种挑战相关的炎症和重塑反应。
从六名表型良好的 CRSwNP 患者（正在接受功能性内镜鼻窦手术）的鼻息肉组织中提取外植体，用 1、10 和 100μg/ml 的交链孢霉、黑曲霉、枝孢菌和青霉刺激，并与未受刺激的息肉组织作为对照。酶联免疫吸附试验（ELISA）用于测量息肉上清液中促炎细胞因子白细胞介素-6（IL-6）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）和肿瘤坏死因子-α（TNF-α）；以及促重塑细胞因子转化生长因子-β1（TGF-β1）和碱性成纤维细胞生长因子（bFGF）的水平。
黑曲霉刺激增加了促炎细胞因子 TNF-α、GM-CSF 和 IL-6，而对重塑细胞因子 bFGF 和 TGF-β1 几乎没有影响。相比之下，枝孢菌、交链孢霉和青霉刺激减少了促炎细胞因子 TNF-α和 IL-6，但诱导了重塑细胞因子 TGF-β1 和 bFGF 的剂量依赖性增加。
本研究表明，常见的空气传播真菌对上呼吸道炎症和重塑反应具有特定的影响。这些发现为真菌在 CRS 中具有疾病修饰作用提供了进一步的免疫学证据。
