Interleukin-13 Promotes Susceptibility to Chlamydial Infection of the Respiratory and Genital Tracts

Autor: Kenneth W. Beagley, Paul S. Foster, Alison J. Carey, Gerard E. Kaiko, Kelly L. Asquith, Philip M. Hansbro, Jay C. Horvat
Rok vydání: 2011
Předmět:
CD4-Positive T-Lymphocytes
Immunology/Innate Immunity
Vaginal Diseases
Microbiology/Innate Immunity
Respiratory Medicine/Respiratory Infections
Mice
Immunology/Reproductive Immunology
lcsh:QH301-705.5
Lung
Respiratory Tract Infections
Mice
Knockout
Mice
Inbred BALB C
Interleukin-13
Respiratory tract infections
060500 MICROBIOLOGY
Microbiology/Immunity to Infections
110800 MEDICAL MICROBIOLOGY
Interleukin-10
Interleukin 10
medicine.anatomical_structure
Interleukin 13
Female
Disease Susceptibility
medicine.symptom
Immunology/Allergy and Hypersensitivity
Microbiology/Cellular Microbiology and Pathogenesis
Research Article
lcsh:Immunologic diseases. Allergy
Chlamydia muridarum
T cell
Immunology
Respiratory Medicine/Asthma
Inflammation
Biology
Microbiology
Interferon-gamma
Immune system
Immunity
Immunology/Immunity to Infections
Virology
Genetics
medicine
Animals
110700 IMMUNOLOGY
Molecular Biology
Macrophages
Epithelial Cells
Chlamydia Infections
biology.organism_classification
Immunity
Innate
Bacterial Load
lcsh:Biology (General)
Parasitology
lcsh:RC581-607
Zdroj: PLoS Pathogens
PLoS Pathogens, Vol 7, Iss 5, p e1001339 (2011)
Popis: Chlamydiae are intracellular bacteria that commonly cause infections of the respiratory and genital tracts, which are major clinical problems. Infections are also linked to the aetiology of diseases such as asthma, emphysema and heart disease. The clinical management of infection is problematic and antibiotic resistance is emerging. Increased understanding of immune processes that are involved in both clearance and immunopathology of chlamydial infection is critical for the development of improved treatment strategies. Here, we show that IL-13 was produced in the lungs of mice rapidly after Chlamydia muridarum (Cmu) infection and promoted susceptibility to infection. Wild-type (WT) mice had increased disease severity, bacterial load and associated inflammation compared to IL-13 deficient (−/−) mice as early as 3 days post infection (p.i.). Intratracheal instillation of IL-13 enhanced bacterial load in IL-13−/− mice. There were no differences in early IFN-g and IL-10 expression between WT and IL-13−/− mice and depletion of CD4+ T cells did not affect infection in IL-13−/− mice. Collectively, these data demonstrate a lack of CD4+ T cell involvement and a novel role for IL-13 in innate responses to infection. We also showed that IL-13 deficiency increased macrophage uptake of Cmu in vitro and in vivo. Moreover, the depletion of IL-13 during infection of lung epithelial cells in vitro decreased the percentage of infected cells and reduced bacterial growth. Our results suggest that enhanced IL-13 responses in the airways, such as that found in asthmatics, may promote susceptibility to chlamydial lung infection. Importantly the role of IL-13 in regulating infection was not limited to the lung as we showed that IL-13 also promoted susceptibility to Cmu genital tract infection. Collectively our findings demonstrate that innate IL-13 release promotes infection that results in enhanced inflammation and have broad implications for the treatment of chlamydial infections and IL-13-associated diseases.
Author Summary Chlamydial infections are a common cause of respiratory, genital tract and eye diseases, and infections are clinically associated with the aetiology of asthma, emphysema, heart disease and Alzheimer's. However, it is not known what immune factors regulate enhanced susceptibility to infection and immunopathology. In this study we have investigated the role of the immune factor, interleukin-13 (IL-13), in C. muridarum infections in mice. IL-13 is produced rapidly after respiratory infection in normal mice. However, mice deficient in IL-13 have reduced clinical symptoms and numbers of C. muridarum in their lungs after infection. The immune cells of mice deficient in IL-13 phagocytose more C. muridarum and their lung cells have less infection. The role of IL-13 is not restricted to the lung as IL-13-deficient mice have significantly lower levels of bacterial replication and more mild disease during genital tract infection. Our results suggest that IL-13 responses enhance chlamydial infections and that this factor may be a new therapeutic target for the treatment of disease.
Databáze: OpenAIRE
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