Th17 cytokine deficiency in patients with Aspergillus skull base osteomyelitis

Corine E Delsing, Katharina L Becker, Anna Simon, Bart Jan Kullberg, Chantal P Bleeker-Rovers, Frank L van de Veerdonk, Mihai G Netea

Fungal skull base osteomyelitis (SBO) is a severe complication of otitis externa or sinonasal infection, and is mainly caused by Aspergillus species. Here we investigate innate and adaptive immune responses in patients with Aspergillus SBO to identify defects in the immune response that could explain the susceptibility to this devastating disease. Peripheral blood mononuclear cells isolated from six patients with Aspergillus SBO and healthy volunteers were stimulated with various microbial stimuli, among which also the fungal pathogens Candida albicans and Aspergillus fumigatus. The proinflammatory cytokines IL-6, TNFα and IL-1β, and the T-helper cell-derived cytokines IFNγ, IL-17 and IL-22 were measured in cell culture supernatants by ELISA. Proinflammatory cytokine responses did not differ between SBO patients and healthy volunteers. The Candida- and Aspergillus-specific Th17 response (production of IL-17 and IL-22) was significantly decreased in the SBO patients compared to healthy individuals, while Th1 cytokine response (IFNγ production) did not differ between the two groups. We show that patients with Aspergillus skull base osteomyelitis infection have specific defects in Th17 responses. Since IL-17 and IL-22 are important for stimulating antifungal host defense, we hypothesize that strategies that have the ability to improve IL-17 and IL-22 production may be useful as adjuvant immunotherapy in patients with Aspergillus SBO.