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Visualization of IL-22-expressing Lymphocytes Using Reporter Mice
Published on: January 25, 2017
IL-22 Promotes IFN-γ-Mediated Immunity against Histoplasma capsulatum Infection
Morgana K B Prado1,2, Caroline Fontanari1, Camila O S Souza1,2
1Departamento de Análises Clínicas, Toxicológicas e Bromatológicas da Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo 14040-903, Brazil.
Abstract:
Histoplasma capsulatum is the agent of histoplasmosis, one of the most frequent mycoses in the world. The infection initiates with fungal spore inhalation, transformation into yeasts in the lungs and establishment of a granulomatous disease, which is characterized by a Th1 response. The production of Th1 signature cytokines, such as IFN-γ, is crucial for yeast clearance from the lungs, and to prevent dissemination. Recently, it was demonstrated that IL-17, a Th17 signature cytokine, is also important for fungal control, particularly in the absence of Th1 response. IL-22 is another cytokine with multiple functions on host response and disease progression. However, little is known about the role of IL-22 during histoplasmosis. In this study, we demonstrated that absence of IL-22 affected the clearance of yeasts from the lungs and increased the spreading to the spleen. In addition, IL-22 deficient mice (Il22-/-) succumbed to infection, which correlated with reductions in the numbers of CD4+ IFN-γ+ T cells, reduced IFN-γ levels, and diminished nitric oxide synthase type 2 (NOS2) expression in the lungs. Importantly, treatment with rIFN-γ mitigated the susceptibility of Il22-/- mice to H. capsulatum infection. These data indicate that IL-22 is crucial for IFN-γ/NO production and resistance to experimental histoplasmosis.
Insights
Interleukin-22 (IL-22) is vital for controlling Histoplasma capsulatum infection by promoting fungal clearance and preventing disease spread. Its absence increases susceptibility to histoplasmosis.
Area of Science:
- Immunology
- Mycology
- Infectious Diseases
Background:
- Histoplasmosis, caused by *Histoplasma capsulatum*, is a common fungal infection worldwide.
- The immune response, particularly Th1 cytokines like IFN-γ, is crucial for controlling fungal load and preventing dissemination.
- The role of Interleukin-22 (IL-22) in histoplasmosis remains largely unexplored.
Purpose of the Study:
- To investigate the role of IL-22 in the host immune response to *Histoplasma capsulatum* infection.
- To determine the impact of IL-22 deficiency on fungal clearance and dissemination.
- To elucidate the mechanisms by which IL-22 influences resistance to experimental histoplasmosis.
Main Methods:
- Utilized IL-22 deficient mice (*Il22*-/-) to study experimental histoplasmosis.
- Assessed fungal burden in lungs and spleen.
- Quantified immune cell populations (CD4+ IFN-γ+ T cells), cytokine levels (IFN-γ), and gene expression (NOS2).
- Investigated the therapeutic potential of recombinant IFN-γ (rIFN-γ) in IL-22 deficient mice.
Main Results:
- Absence of IL-22 impaired yeast clearance from the lungs and promoted fungal spread to the spleen.
- IL-22 deficient mice exhibited increased susceptibility to infection, succumbing to the disease.
- Reduced numbers of CD4+ IFN-γ+ T cells, lower IFN-γ levels, and diminished NOS2 expression were observed in IL-22 deficient mice.
- Treatment with rIFN-γ partially rescued IL-22 deficient mice from infection-induced mortality.
Conclusions:
- IL-22 plays a critical role in host defense against *Histoplasma capsulatum*.
- IL-22 is essential for effective IFN-γ and nitric oxide production during histoplasmosis.
- IL-22 contributes significantly to resistance against experimental histoplasmosis, highlighting its importance in fungal immunity.
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