Interleukin-13 promotes susceptibility to chlamydial infection of the respiratory and genital tracts.
Interleukin-13 promotes susceptibility to chlamydial infection of the respiratory and genital tracts.
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DOI：
10.1371/journal.ppat.1001339
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发表时间：
2011-05
期刊：
影响因子：
6.7
通讯作者：
Foster PS
中科院分区：
文献类型：
--
作者：
Asquith KL;Horvat JC;Kaiko GE;Carey AJ;Beagley KW;Hansbro PM;Foster PS
衣原体是细胞内细菌，通常引起呼吸道和生殖道感染，这是主要的临床问题。感染还与哮喘、肺气肿和心脏病等疾病的病因有关。感染的临床管理是有问题的，抗生素耐药性正在出现。增加对衣原体感染的清除和免疫病理所涉及的免疫过程的了解对于改进治疗策略的发展至关重要。本研究表明，小鼠感染衣原体（Chlamydia muridarum, Cmu）后，肺中迅速产生IL-13，并促进对感染的易感性。野生型（WT）小鼠早在感染后3天（p.i.）就比IL-13缺陷（- / -）小鼠的疾病严重程度、细菌负荷和相关炎症增加。气管内灌注IL-13可提高IL-13−/−小鼠的细菌负荷。WT和IL-13−/−小鼠的早期IFN-g和IL-10表达无差异，CD4+ T细胞的消耗不影响IL-13−/−小鼠的感染。总的来说，这些数据表明缺乏CD4+ T细胞参与和IL-13在先天感染反应中的新作用。我们还发现IL-13缺乏增加了巨噬细胞对Cmu的体外和体内摄取。此外，体外肺上皮细胞感染过程中IL-13的缺失降低了感染细胞的百分比，减少了细菌的生长。我们的研究结果表明，气道中IL-13反应的增强，如哮喘患者，可能会促进对衣原体肺部感染的易感性。重要的是，IL-13在调节感染中的作用并不局限于肺部，因为我们发现IL-13也促进了对Cmu生殖道感染的易感性。总的来说，我们的研究结果表明，先天IL-13释放促进感染，导致炎症增强，并对衣原体感染和IL-13相关疾病的治疗具有广泛的意义。衣原体感染是呼吸道、生殖道和眼部疾病的常见病因，在临床上，感染与哮喘、肺气肿、心脏病和阿尔茨海默氏症的病因有关。然而，目前尚不清楚是什么免疫因子调节了对感染和免疫病理的易感性。在这项研究中，我们研究了免疫因子，白细胞介素-13 (IL-13)，在小鼠muridarum感染中的作用。IL-13在正常小鼠呼吸道感染后迅速产生。然而，缺乏IL-13的小鼠感染后，临床症状和肺部的muridarum数量减少。缺乏IL-13的小鼠免疫细胞对毒梭菌的吞噬较多，肺细胞感染较少。IL-13的作用并不局限于肺部，因为IL-13缺陷小鼠在生殖道感染期间细菌复制水平显著降低，疾病更轻微。我们的研究结果表明，IL-13反应增强了衣原体感染，该因子可能是治疗疾病的新靶点。
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. 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.
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