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Evolution of the Immune Response to Chronic Airway Colonization with Aspergillus fumigatus Hyphae

机译：烟曲霉菌丝对慢性气道定植免疫反应的演变

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Airway colonization by the mold Aspergillus fumigatus is common in patients with underlying lung disease and is associated with chronic airway inflammation. Studies probing the inflammatory response to colonization with A. fumigatus hyphae have been hampered by the lack of a model of chronic colonization in immunocompetent mice. By infecting mice intratracheally with conidia embedded in agar beads (Af beads), we have established an in vivo model to study the natural history of airway colonization with live A. fumigatus hyphae. Histopathological examination and galactomannan assay of lung homogenates demonstrated that hyphae exited beads and persisted in the lungs of mice up to 28 days postinfection without invasive disease. Fungal lesions within the airways were surrounded by a robust neutrophilic inflammatory reaction and peribronchial infiltration of lymphocytes. Whole-lung cytokine analysis from Af bead-infected mice revealed an increase in proinflammatory cytokines and chemokines early in infection. Evidence of a Th2 type response was observed only early in the course of colonization, including increased levels of interleukin-4 (IL-4), elevated IgE levels in serum, and a mild increase in airway responsiveness. Pulmonary T cell subset analysis during infection mirrored these results with an initial transient increase in IL-4-producing CD4+ T cells, followed by a rise in IL-17 and Foxp3+ cells by day 14. These results provide the first report of the evolution of the immune response to A. fumigatus hyphal colonization.
机译：烟曲霉菌在气道中的定殖在患有基础肺部疾病的患者中很普遍，并且与慢性气道炎症相关。由于缺乏能胜任免疫力的小鼠的慢性定殖模型，阻碍了对烟曲霉菌丝定殖的炎症反应的研究受到了阻碍。通过在气管内用琼脂珠（Af珠）中嵌入的分生孢子感染小鼠，我们建立了体内模型，以研究活烟曲霉菌丝对气道定植的自然史。肺匀浆的组织病理学检查和半乳甘露聚糖测定表明，菌丝离开珠子并在感染后28天内持续存在于小鼠的肺中，而没有侵袭性疾病。气道内的真菌病变被强烈的嗜中性炎症反应和淋巴细胞的支气管周浸润所包围。 Af珠感染小鼠的全肺细胞因子分析表明，感染初期促炎细胞因子和趋化因子增加。仅在定殖过程的早期就观察到Th2型应答的证据，包括白介素4（IL-4）水平升高，血清IgE水平升高以及气道响应性轻度升高。在感染过程中进行的肺T细胞亚群分析反映了这些结果，即在产生IL-4的CD4 + T细胞中最初出现短暂的增加，然后在第14天时IL-17和Foxp3 +细胞的增加。对烟曲霉菌丝菌落定植的免疫反应。

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