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Title (Primary) IL-13 induces disease-promoting type 2 cytokines, alternatively activated macrophages and allergic inflammation during pulmonary infection of mice with Cryptococcus neoformans
Author Müller, U.; Stenzel, W.; Köhler, G.; Werner, C.; Polte, T.; Hansen, G.; Schütze, N.; Straubinger, R.K.; Blessing, M.; McKenzie, A.N.J.; Brombacher, F.; Alber, G.;
Journal Journal of Immunology
Year 2007
Department IMMU;
Volume 179
Issue 8
Language englisch;
Abstract In the murine model of Cryptococcus neoformans infection Th1 (IL-12/IFN-) and Th17 (IL-23/IL-17) responses are associated with protection, whereas an IL-4-dependent Th2 response exacerbates disease. To investigate the role of the Th2 cytokine IL-13 during pulmonary infection with C. neoformans, IL-13-overexpressing transgenic (IL-13Tg+), IL-13-deficient (IL-13-/-), and wild-type (WT) mice were infected intranasally. Susceptibility to C. neoformans infection was found when IL-13 was induced in WT mice or overproduced in IL-13Tg+ mice. Infected IL-13Tg+ mice had a reduced survival time and higher pulmonary fungal load as compared with WT mice. In contrast, infected IL-13-/- mice were resistant and 89% of these mice survived the entire period of the experiment. Ag-specific production of IL-13 by susceptible WT and IL-13Tg+ mice was associated with a significant type 2 cytokine shift but only minor changes in IFN- production. Consistent with enhanced type 2 cytokine production, high levels of serum IgE and low ratios of serum IgG2a/IgG1 were detected in susceptible WT and IL-13Tg+ mice. Interestingly, expression of IL-13 by susceptible WT and IL-13Tg+ mice was associated with reduced IL-17 production. IL-13 was found to induce formation of alternatively activated macrophages expressing arginase-1, macrophage mannose receptor (CD206), and YM1. In addition, IL-13 production led to lung eosinophilia, goblet cell metaplasia and elevated mucus production, and enhanced airway hyperreactivity. This indicates that IL-13 contributes to fatal allergic inflammation during C. neoformans infection.
ID 2104
Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=2104
Müller, U., Stenzel, W., Köhler, G., Werner, C., Polte, T., Hansen, G., Schütze, N., Straubinger, R.K., Blessing, M., McKenzie, A.N.J., Brombacher, F., Alber, G. (2007):
IL-13 induces disease-promoting type 2 cytokines, alternatively activated macrophages and allergic inflammation during pulmonary infection of mice with Cryptococcus neoformans
J. Immunol. 179 (8), 5367 - 5377