Lung epithelium is the major source of IL-33 and is regulated by IL-33-dependent and IL-33-independent mechanisms in pulmonary cryptococcosis.
Inhalation of the fungus Cryptococcus neoformans (C. neoformans) results in pulmonary cryptococcosis associated with IL-33-dependent type 2 immunity. Lung epithelium represents the initial contact site of infection. The role of IL-33 in type 2 immunity has been analyzed, but the source of this cytokine and its effect on lung epithelial cell function in pulmonary cryptococcosis remained unclear. In mice infected with C. neoformans, we identified alveolar type 2 epithelial cells as major source of IL-33. On both, IL-33-positive and IL-33-negative epithelial cells, IL-33 receptor expression was detectable. Therefore, we studied the role of IL-33 receptor expression for IL-33 synthesis during fungal infection on lung epithelial cells and found no auto-/paracrine IL-33 induction. Next, the effect of IL-33 on epithelial E-cadherin expression, a cell-to-cell adhesion molecule, was analyzed. Fungal infection resulted in E-cadherin downregulation in an IL-33-dependent manner on pulmonary epithelial cells both at the single-cell and at the population level. On the other hand, epithelial cells from infected mice upregulated surfactant protein C (SP-C) and CXCL15 mRNA production together with but independently of IL-33. In conclusion, lung epithelium represents a significant source of IL-33 in pulmonary cryptococcosis and is regulated in an IL-33-dependent but also IL-33-independent manner.
Institute of Immunology/Molecular Pathogenesis, Center for Biotechnology and Biomedicine, College of Veterinary Medicine, University of Leipzig, An den Tierkliniken 11, D - 04103 Leipzig, Germany.
Laura
L
Heyen
Institute of Immunology/Molecular Pathogenesis, Center for Biotechnology and Biomedicine, College of Veterinary Medicine, University of Leipzig, An den Tierkliniken 11, D - 04103 Leipzig, Germany.
Uwe
U
Müller
Institute of Immunology/Molecular Pathogenesis, Center for Biotechnology and Biomedicine, College of Veterinary Medicine, University of Leipzig, An den Tierkliniken 11, D - 04103 Leipzig, Germany.
Sabine
S
Siegemund
Institute of Immunology/Molecular Pathogenesis, Center for Biotechnology and Biomedicine, College of Veterinary Medicine, University of Leipzig, An den Tierkliniken 11, D - 04103 Leipzig, Germany.
Bianca
B
Schulze
Institute of Immunology/Molecular Pathogenesis, Center for Biotechnology and Biomedicine, College of Veterinary Medicine, University of Leipzig, An den Tierkliniken 11, D - 04103 Leipzig, Germany.
Martina
M
Protschka
Institute of Immunology/Molecular Pathogenesis, Center for Biotechnology and Biomedicine, College of Veterinary Medicine, University of Leipzig, An den Tierkliniken 11, D - 04103 Leipzig, Germany alber@rz.uni-leipzig.de.
Gottfried
G
Alber
Institute of Immunology/Molecular Pathogenesis, Center for Biotechnology and Biomedicine, College of Veterinary Medicine, University of Leipzig, An den Tierkliniken 11, D - 04103 Leipzig, Germany.
Daniel
D
Piehler
Cryptococcus neoformans; IL-33; airway epithelial cells; mouse; pulmonary infection