ANALYSIS of INTERLEUKIN-33 PRODUCING CELLS AFTER INFECTION with CRYPTOCOCCUS NEOFORMANS in an EXPERIMENTAL MOUSE MODEL

The opportunistic fungal pathogen Cryptococcus neoformans causes an asymptomatic respiratory infection in immunocompetent individuals resulting in growth control. In contrast, immuno-suppression, e.g. in AIDS, promotes fungal proliferation and haematogenous dissemination, ultimately leading to a life-threatening meningitis. Haematogenous dissemination of Cryptococcus is favored by a type 2 immune response characterized by key cytokines interleukin (IL)-4, -5 and -13, non-protective alternative activation of pulmonary macrophages and eosinophil recruitment, thus closely resembling features of allergic airway inflammation (AAI). A type 2-biased immune response may even occur in immunocompetent individuals and therefore predispose for the development of airway inflammation and finally allergic asthma. Yet, the precise mechanism of type 2 cytokine induction is not known in pulmonary cryptococcosis.

In our study we focus on the cytokine IL-33 which can be an early inducer of type 2 immunity. Therefore, we performed a kinetic analysis of intranasally infected IL-33 citrine reporter mice with several time points of analysis up to 70 days post infection (dpi). We identified different cell types in the lung that became citrine positive, indicating il33 expression, during cryptococcal infection using flow cytometry and immunofluorescence microscopy. In our study lung epithelial cells represent the main citrine positive population. The lung epithelium is the first contact site for lower respiratory tract infections in general. A detailed understanding how respiratory epithelium contribute to Th2 immune response during an infection with Cryptococcus could provide new opportunities for early, effective therapy not only for pulmonary cryptococcosis but hopefully AAI in general.