Müller, Uwe;
Stenzel, Werner;
Köhler, Gabriele;
Werner, Christoph;
Polte, Tobias;
Hansen, Gesine;
Schütze, Nicole;
Straubinger, Reinhard K.;
Blessing, Manfred;
McKenzie, Andrew N. J.;
Brombacher, Frank;
Alber, Gottfried
IL-13 Induces Disease-Promoting Type 2 Cytokines, Alternatively Activated Macrophages and Allergic Inflammation during Pulmonary Infection of Mice with Cryptococcus neoformans
You can manage bookmarks using lists, please log in to your user account for this.
Media type:
E-Article
Title:
IL-13 Induces Disease-Promoting Type 2 Cytokines, Alternatively Activated Macrophages and Allergic Inflammation during Pulmonary Infection of Mice with Cryptococcus neoformans
Contributor:
Müller, Uwe;
Stenzel, Werner;
Köhler, Gabriele;
Werner, Christoph;
Polte, Tobias;
Hansen, Gesine;
Schütze, Nicole;
Straubinger, Reinhard K.;
Blessing, Manfred;
McKenzie, Andrew N. J.;
Brombacher, Frank;
Alber, Gottfried
Published:
The American Association of Immunologists, 2007
Published in:
The Journal of Immunology, 179 (2007) 8, Seite 5367-5377
Language:
English
DOI:
10.4049/jimmunol.179.8.5367
ISSN:
0022-1767;
1550-6606
Origination:
Footnote:
Description:
<jats:title>Abstract</jats:title>
<jats:p>In the murine model of Cryptococcus neoformans infection Th1 (IL-12/IFN-γ) 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-γ 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.</jats:p>