IL-13 Induces Disease-Promoting Type 2 Cytokines, Alternatively Activated Macrophages and Allergic Inflammation during Pulmonary Infection of Mice with Cryptococcus neoformans

  • Müller U
  • Stenzel W
  • Köhler G
  • et al.
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Abstract

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.

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APA

Müller, U., Stenzel, W., Köhler, G., Werner, C., Polte, T., Hansen, G., … 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. The Journal of Immunology, 179(8), 5367–5377. https://doi.org/10.4049/jimmunol.179.8.5367

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