Department of Clinical Sciences Lund, Respiratory Medicine & Allergology, Skåne University Hospital, Lund University, Lund, Sweden.
Infection Medicine, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Lund, Sweden.
Allergy. 2019 Apr;74(4):663-674. doi: 10.1111/all.13646. Epub 2018 Nov 19.
In atopic asthma, chronic Th2-biased inflammation is associated with an increased risk of pneumococcal infection. The anionic phosphoglycoprotein osteopontin (OPN) is highly expressed in asthma and has been ascribed several roles during inflammation. This study aimed to investigate whether OPN affects inflammation and vulnerability to pneumococcal infection in atopic asthma.
House dust mite (HDM) extract was used to induce allergic airway inflammation in both wild-type (Spp1 ) and OPN knockout (Spp1 ) C57BL/6J mice, and the airway was then infected with Streptococcus pneumoniae. Parameters reflecting inflammation, tissue injury, and bacterial burden were measured. In addition, samples from humans with allergic asthma were analyzed.
Both allergen challenge in individuals with allergic asthma and the intranasal instillation of HDM in mice resulted in increased OPN levels in bronchoalveolar lavage fluid (BALF). More immune cells (including alveolar macrophages, neutrophils, eosinophils, and lymphocytes) and higher levels of proinflammatory cytokines were found in Spp1 mice than in Spp1 mice. Moreover, OPN-deficient mice exhibited increased levels of markers reflecting tissue injury. Upon infection with S. pneumoniae, Spp1 mice with allergic airway inflammation had a significantly lower bacterial burden in both BALF and lung tissue than did Spp1 mice. Furthermore, Spp1 mice had higher levels of cytokines and immune cells in BALF than did Spp1 mice.
OPN reduces inflammation, decreases tissue injury, and reduces bacterial loads during concurrent pneumococcal infection and allergic airway inflammation in a murine model. These findings suggest that OPN significantly affects vulnerability to pneumococcal infection in atopic asthma.
在特应性哮喘中，慢性 Th2 偏向性炎症与肺炎球菌感染的风险增加相关。阴离子磷酸糖蛋白骨桥蛋白（OPN）在哮喘中高度表达，并在炎症过程中具有多种作用。本研究旨在探讨 OPN 是否影响特应性哮喘中的炎症和肺炎球菌易感性。
使用屋尘螨（HDM）提取物在野生型（Spp1）和 OPN 敲除（Spp1）C57BL/6J 小鼠中诱导过敏性气道炎症，然后用肺炎链球菌感染气道。测量反映炎症、组织损伤和细菌负荷的参数。此外，还分析了患有过敏性哮喘的人类的样本。
过敏性哮喘患者的过敏原挑战和小鼠的 HDM 鼻内滴注均导致支气管肺泡灌洗液（BALF）中 OPN 水平升高。Spp1 小鼠中发现更多的免疫细胞（包括肺泡巨噬细胞、中性粒细胞、嗜酸性粒细胞和淋巴细胞）和更高水平的促炎细胞因子。此外，OPN 缺陷型小鼠表现出更高水平的反映组织损伤的标志物。在感染肺炎链球菌后，患有过敏性气道炎症的 Spp1 小鼠的 BALF 和肺组织中的细菌负荷明显低于 Spp1 小鼠。此外，Spp1 小鼠的 BALF 中的细胞因子和免疫细胞水平高于 Spp1 小鼠。
OPN 可减少肺炎球菌感染和过敏性气道炎症并存时的炎症、减少组织损伤和降低细菌负荷。这些发现表明 OPN 可显著影响特应性哮喘中的肺炎球菌易感性。
