Linking early IL-4 producing cell types with allergic pulmonary inflammation induced by infection with Cryptococcus neoformans
Final Report Abstract
In pulmonary cryptococcosis a Th2 response is detrimental for the host, concomitant with bronchoconstriction, mucus production by goblet cells, eosinophilia and alternative activation of macrophages. These factors are the base for an uncontrolled fungal growth with dissemination to peripheral organs, especially the central nervous system with inflammation of the meninges. Our findings show that in this fungal infection the most important cells to induce a Th2 response driven by IL-4 are Th2 cells and eosinophils. IL-4 is able to induce alternative activation of macrophages, one of the major pathological mechanisms in pulmonary cryptococcosis, as we had shown earlier. Whereas Th2 cells can induce aaMph, ILC2 cells seem uncapable of inducing alternative activation of macrophages. Another factor seen in mice susceptible for pulmonary cryptococcosis is the upregulation of IgE production during infection. Our data indicate that IgE is irrelevant for pathogenesis during pulmonary cryptococcosis, hence it is rather a marker for susceptibility than a pathogenesis factor.
Publications
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Eosinophils contribute to IL-4 production and shape the T-helper cytokine profile and inflammatory response in pulmonary cryptococcosis. Am J Pathol. 2011 Aug;179(2):733-44
Piehler D, Stenzel W, Grahnert A, Held J, Richter L, Köhler G, Richter T, Eschke M, Alber G, Müller U
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The IL-33 receptor (ST2) regulates early IL-13 production in fungus-induced allergic airway inflammation. Mucosal Immunol. 2015 Nov 11
Piehler D, Eschke M, Schulze B, Protschka M, Müller U, Grahnert A, Richter T, Heyen L, Köhler G, Brombacher F, Alber G
