https://ror.org/01z7r7q48 Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA
Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Life Sci Alliance. 2024 Aug 12;7(11). doi: 10.26508/lsa.202402618. Print 2024 Nov.
Recurrent infections are a hallmark of STAT3 dominant-negative hyper-IgE syndrome (STAT3 HIES), a rare immunodeficiency syndrome previously known as Jobs syndrome, along with elevated IgE levels and impaired neutrophil function. We have been developing nanoparticles with neutrophil trophism that home to the sites of infection via these first-responder leukocytes, named neutrophil-avid nanocarriers (NANs). Here, we demonstrate that human neutrophils can phagocytose nanogels (NGs), a type of NAN, with enhanced uptake after particle serum opsonization, comparing neutrophils from healthy individuals to those with STAT3 HIES, where both groups exhibit NG uptake; however, the patient group showed reduced phagocytosis efficiency with serum-opsonized NANs. Proteomic analysis of NG protein corona revealed complement components, particularly C3, as predominant in both groups. Difference between groups includes STAT3 HIES samples with higher neutrophil protein and lower acute-phase protein expression. The study suggests that despite neutrophil dysfunction in STAT3 HIES, NANs have potential for directed delivery of cargo therapeutics to improve neutrophil infection clearance.
复发性感染是 STAT3 显性负性高免疫球蛋白 E 综合征（STAT3 HIES）的一个标志，STAT3 HIES 是一种罕见的免疫缺陷综合征，以前也被称为 Jobs 综合征，同时伴有 IgE 水平升高和中性粒细胞功能受损。我们一直在开发具有嗜中性粒细胞趋化性的纳米粒子，这些纳米粒子通过这些第一反应性白细胞（称为嗜中性粒细胞亲和纳米载体[NANs]）归巢到感染部位。在这里，我们证明人类中性粒细胞可以吞噬纳米凝胶（NGs），一种 NAN，在颗粒血清调理后摄取增强，将健康个体的中性粒细胞与 STAT3 HIES 中的中性粒细胞进行比较，两组都表现出 NG 摄取；然而，患者组的血清调理 NAN 的吞噬效率降低。NG 蛋白衣壳的蛋白质组学分析显示补体成分，特别是 C3，在两组中均占主导地位。组间差异包括 STAT3 HIES 样本中中性粒细胞蛋白表达升高和急性期蛋白表达降低。该研究表明，尽管 STAT3 HIES 中的中性粒细胞功能障碍，NAN 仍有可能将货物治疗剂靶向递送至改善中性粒细胞感染清除。
