Ripamonti Chiara, Bishop Lisa R, Kovacs Joseph A
Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Critical Care Medicine Department, NIH Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
Infect Immun. 2017 Jun 20;85(7). doi: 10.1128/IAI.00434-16. Print 2017 Jul.
remains an important pathogen of immunosuppressed patients, causing a potentially life-threatening pneumonia. Despite its medical importance, the immune responses required to control infection, including the role of interleukin-17 (IL-17), which is important in controlling other fungal infections, have not been clearly defined. Using flow cytometry and intracellular cytokine staining after stimulation with phorbol myristate acetate and ionomycin, we examined gamma interferon (IFN-γ), IL-4, IL-5, and IL-17 production by lung lymphocytes in immunocompetent C57BL/6 mice over time following infection with We also examined the clearance of infection in IL-17A-deficient mice. The production of both IFN-γ and IL-17 by pulmonary lymphocytes increased during infection, with maximum production at approximately days 35 to 40, coinciding with peak levels in the lungs, while minimal changes were seen in IL-4- and IL-5-positive cells. The proportion of cells producing IFN-γ was consistently higher than for cells producing IL-17, with peak levels of ∼25 to 30% of CD3 T cells for the former compared to ∼15% for the latter. Both CD4 T cells and γδ T cells produced IL-17. Administration of anti-IFN-γ antibody led to a decrease in IFN-γ-positive cells, and an increase in IL-5-positive cells, but did not impact clearance of infection. Despite the increases in IL-17 production during infection, IL-17A-deficient mice cleared infection with kinetics similar to C57BL/6 mice. Thus, while IL-17 production in the lungs is increased during infection in immunocompetent mice, IL-17A is not required for control of infection.
仍然是免疫抑制患者的一种重要病原体，可导致潜在的危及生命的肺炎。尽管其具有医学重要性，但控制感染所需的免疫反应，包括在控制其他真菌感染中起重要作用的白细胞介素-17（IL-17）的作用，尚未明确界定。在用佛波酯肉豆蔻酸酯和离子霉素刺激后，使用流式细胞术和细胞内细胞因子染色，我们检测了免疫健全的C57BL/6小鼠在感染后不同时间肺淋巴细胞产生的γ干扰素（IFN-γ）、IL-4、IL-5和IL-17。我们还检测了IL-17A缺陷小鼠中该感染的清除情况。在感染期间，肺淋巴细胞产生的IFN-γ和IL-17均增加，在大约第35至40天达到最大产量，这与肺中该菌的峰值水平一致，而IL-4和IL-5阳性细胞的变化最小。产生IFN-γ的细胞比例始终高于产生IL-17的细胞，前者CD3 T细胞的峰值水平约为25%至30%，而后者约为15%。CD4 T细胞和γδ T细胞均产生IL-17。给予抗IFN-γ抗体导致IFN-γ阳性细胞减少，IL-5阳性细胞增加，但不影响该菌感染的清除。尽管在感染期间IL-17的产生增加，但IL-17A缺陷小鼠清除该菌感染的动力学与C57BL/6小鼠相似。因此，虽然在免疫健全的小鼠感染期间肺中IL-17的产生增加，但控制该菌感染不需要IL-17A。
