Diverse phenotypes and endotypes of fungus balls caused by mixed bacterial colonization in chronic rhinosinusitis.

Abstract

The pathogenic roles of fungus and bacteria in chronic rhinosinusitis (CRS) remain unclear. Recently, we described the bacterial ball, which is distinct from the fungus ball, as an unusual phenotype of bacterial infection. In this study, we investigated the clinical, histopathologic, and immunologic characteristics of sinonasal microorganic materials, including fungus ball and bacterial ball. In this study, we enrolled 80 CRS patients with sinonasal microorganic materials and 10 control subjects who underwent skull base surgery or endoscopic dacryocystorhinostomy and had no signs or symptoms of nasal inflammation. All specimens were stained with hematoxylin-eosin, Gomori-methenamine-silver, and Gram stain to identify fungal organisms and Gram-positive/negative bacterial colonies. The expression of tumor necrosis factor (TNF)-α; interleukin (IL)-1β; S100A7; S100A8/A9; and short, palate, lung, and nasal epithelial clone 1 (SPLUNC1) were evaluated by enzyme-linked immunosorbent assay using sinus lavage fluid. We histologically classified sinonasal microorganic materials into the following 4 groups: fungus ball (n = 45); bacterial ball (n = 6); mixed ball (formed by a mixture of fungus and bacteria, n = 27); and double ball (formed by separate fungal and bacterial balls, n = 2). Compared with the fungus ball, the mixed ball was more frequently detected in immunocompromised patients (p < 0.0001). In addition, TNF-α expression was significantly higher in fungus and mixed balls than in control, whereas the mixed ball showed higher expression of IL-1β compared with the fungus ball. Moreover, the expression of S100A7 and S100A8/A9 protein in the mixed ball was significantly decreased when compared with the fungus ball, whereas there was no significant difference in SPLUNC1 expression between fungus and mixed balls. Our findings suggest that fungal and bacterial interactions are diverse in CRS. Specifically, the mixed ball is prevalent in CRS with an immunocompromised state and it may decrease epithelial barrier function.