A novel insight into the immunologic basis of chronic granulomatous invasive fungal rhinosinusitis

Abstract

Background: Chronic granulomatous invasive fungal rhinosinusitis (CGIFRS) is a rare disease. The underlying immune responses that drive the development of CGIFRS, as opposed to successful pathogen clearance and controlled inflammation, are not currently known.

Objective: To characterize the immune responses associated with CGIFRS.

Methods: In addition to a battery of basic investigations, more in-depth immunologic testing involves ex vivo whole-blood stimulation with the polyclonal T-cell mitogen phytohemagglutinin and fungal antigens with interleukin (IL) 12, was undertaken to investigate cell-mediated immune responses associated with CGIFRS.

Results: Ex vivo whole-blood stimulation with the polyclonal T-cell mitogen phytohemagglutinin and fungal antigens with IL-12 identified reduced interferon gamma and increased IL-17A levels within the supernatant, which indicated increased in vivo T-helper (Th)17 responses and impaired Th1 responses compared with healthy controls.

Conclusion: These findings suggest that the development of CGIFRS may be associated with an abnormally exaggerated host Th17 response, which caused failure to clear the fungal pathogen with refractory fungal infection of mucosal membranes, resulting in chronic tissue inflammation.

Figure 1.

(a) Coronal T1-weighted magnetic resonance imaging (MRI) at presentation, showing low-intensity concentric mucosal thickening mainly within the left nasal cavity consistent with fungal disease. (b) Coronal T1-weighted MRI 1 year after surgery, showing satisfactory appearances, with no radiologic evidence of recurrent disease.

Figure 2.

Axial computed tomography of the paranasal sinuses, showing demineralization and irregular erosion of the nasal bones.

Figure 3.

(a) Clinical photograph, demonstrating widening of the nasal bridge. (b) An endoscopic photograph of left nasal cavity, demonstrating whitish submucosal lesions, with prominent mucosal telangiectasia on the anterior nasal septum (white asterisk) and the lateral nasal wall (black asterisk).

Figure 4.

(a) Photomicrograph, showing giant cell granulomas (white arrows) with numerous fungal spores (black arrows) and hyphae (blue arrows) (hematoxylin and eosin, original magnification ×40). (b) Photomicrograph, showing fungal hyphae within giant cells staining positively with Grocott stain (original magnification ×40).

Figure 5.

Ex vivo whole-blood interferon γ and interleukin 17A production in response to T-cell mitogen and fungal stimulants versus healthy control. PHA = Phytohemagglutinin; Zym = zymosan.