Interleukin-13 promotes susceptibility to chlamydial infection of the respiratory and genital tracts

• Published in: PLoS pathogens 2011-05, Vol.7 (5), p.e1001339-e1001339
• Main Authors: Asquith, Kelly L, Horvat, Jay C, Kaiko, Gerard E, Carey, Alison J, Beagley, Kenneth W, Hansbro, Philip M, Foster, Paul S
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Animals; Asthma; Bacterial infections; Bacterial Load; Care and treatment; Causes of; CD4-Positive T-Lymphocytes - immunology; Chlamydia; Chlamydia infections; Chlamydia Infections - immunology; Chlamydia Infections - microbiology; Chlamydia muridarum - immunology; Chlamydia muridarum - pathogenicity; Chronic obstructive pulmonary disease; Development and progression; Disease susceptibility; Disease Susceptibility - immunology; Epithelial Cells - immunology; Epithelial Cells - microbiology; Eye diseases; Female; Flow cytometry; Genetic aspects; Health aspects; Immunity, Innate; Immunology/Allergy and Hypersensitivity; Immunology/Immunity to Infections; Immunology/Innate Immunity; Immunology/Reproductive Immunology; Infections; Interferon-gamma - metabolism; Interleukin-10 - metabolism; Interleukin-13 - immunology; Interleukins; Lung - immunology; Lung - microbiology; Lungs; Macrophages - immunology; Macrophages - microbiology; Mice; Mice, Inbred BALB C; Mice, Knockout; Microbiology/Cellular Microbiology and Pathogenesis; Microbiology/Immunity to Infections; Microbiology/Innate Immunity; Nitric oxide; Prevention; Respiratory Medicine/Asthma; Respiratory Medicine/Respiratory Infections; Respiratory Tract Infections - immunology; Respiratory Tract Infections - microbiology; Sexually transmitted diseases; STD; Vaginal Diseases - immunology; Vaginal Diseases - microbiology
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1001339

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.