Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, United States.
Division of Rheumatology, Department of Medicine, Geisel School of Medicine at Dartmouth, Lebanon, NH, United States.
Front Immunol. 2021 Apr 26;12:659523. doi: 10.3389/fimmu.2021.659523. eCollection 2021.
Chronic infection mysteriously occurs in the airways of patients with cystic fibrosis (CF), bronchiectasis (BE), and chronic obstructive pulmonary disease (COPD) in the absence of neutrophil dysfunction or neutropenia and is strongly associated with autoimmunity to bactericidal permeability-increasing protein (BPI). Here, we define a critical role for BPI in immunity against Wild type and BPI-deficient ( mice were infected with , and bacterial clearance, cell infiltrates, cytokine production, and phagocytosis were quantified. mice exhibited a decreased ability to clear in concert with increased neutrophil counts and cytokine release. neutrophils displayed decreased phagocytosis that was corrected by exogenous BPI . Exogenous BPI also enhanced clearance of in -/- mice by increasing uptake by neutrophils in a CD18-dependent manner. These data indicate that BPI plays an essential role in innate immunity against through its opsonic activity and suggest that perturbations in BPI levels or function may contribute to chronic lung infection with .
在不存在中性粒细胞功能障碍或中性粒细胞减少症的情况下，囊性纤维化 (CF)、支气管扩张症 (BE) 和慢性阻塞性肺疾病 (COPD) 患者的气道中会神秘地发生慢性感染，并且与杀菌通透性增加蛋白 (BPI) 的自身免疫强烈相关。在这里，我们定义了 BPI 在对抗野生型和 BPI 缺陷型 () 感染中的关键作用。用 和 感染 野生型和 BPI 缺陷型 () 小鼠，并定量评估细菌清除、细胞浸润、细胞因子产生和吞噬作用。结果显示，与中性粒细胞计数增加和细胞因子释放增加一致，BPI 缺陷型 () 小鼠清除 的能力降低。BPI 缺陷型 () 中性粒细胞的吞噬作用降低，外源性 BPI 可纠正该作用。外源性 BPI 还通过 CD18 依赖性方式增加中性粒细胞摄取，从而增强 对 -/- 小鼠的清除作用。这些数据表明，BPI 通过其调理活性在针对 的先天免疫中发挥重要作用，并表明 BPI 水平或功能的紊乱可能导致慢性肺部感染。
