Peripheral Blood Mononuclear Cells from Allergic Fungal Rhinosinusitis Adults Express a Th2 Cytokine Response to Fungal Antigens

Abstract

Background The etiology of allergic fungal rhinosinusitis (AFRS) remains controversial. Initially thought to represent an immunoglobulin E (IgE)–mediated hypersensitivity to fungal antigens, additional data have implicated other non-IgE and cellular-mediated pathways. The aim of this study was to characterize T-helper type 1 (Th1) and Th2 immune responses of blood lymphocytes from AFRS patients by fungal antigen stimulation to help differentiate these possible pathways. Methods Peripheral blood mononuclear cells (PBMCs) isolated from AFRS patients (n = 10) and healthy controls (HCs; n = 11) were exposed to four different fungal extracts (Alternaria, Aspergillus, Cladosporium, and Penicillium) in duplicate. After a 72-hour incubation, the supernatants were analyzed for cytokine levels of three Th1 (interferon [IFN] gamma, interleukin [IL]-2, and tumor necrosis factor alpha) and three Th2 (IL-10, IL-5, and IL-4) cytokines by cytometric bead array flow cytometry. Serum fungal-specific IgE levels were measured by ImmunoCAP (Pharmacia Diagnostics, Kalamazoo, MI). Results Fungal extracts of Alternaria and Cladosporium stimulated higher levels of IL-5 from PBMCs in AFRS when compared with HCs (p < 0.05). IL-4 was also elevated for Alternaria in AFRS versus HCs (p < 0.05). A skewed Th2 response to fungal antigen exposure was confirmed by an elevated IL-5/IFN-gamma ratio in AFRS subjects (p < 0.05). Initial studies suggest a correlation between percent T-cell activation and IL-5 expression to IgE levels. Fungal antigens stimulated a notable but not statistically significant increase in IL-10 response in HCs. Conclusion In AFRS patients, fungal antigens stimulated T-cell activation, inducing a predominately Th2 immune response. Healthy controls expressed an inhibitory cytokine IL-10 when exposed to these fungal antigens, possibly serving as a protective response.