Shi Ying, Liu Yuan-Yuan, Zhen Yu, Si He-Nan, Guan Meng-Qi, Cui Yan, Li Shan-Shan
Department of Dermatology and Venerology, First Hospital of Jilin University, Changchun, People's Republic of China.
Department of Dermatology and Venerology, First Hospital of Jilin University, Changchun, People's Republic of China.
J Invest Dermatol. 2025 Jul;145(7):1753-1769.e3. doi: 10.1016/j.jid.2024.10.610. Epub 2024 Nov 26.
Low-density neutrophils (LDNs) constitute a distinct subset of neutrophils among PBMCs. They are key mediators in systemic infections, amplifying inflammatory responses and potentially influencing disease severity and chronicity. However, their roles in subcutaneous fungal infections have not been previously investigated. In this study, we observed increased neutrophil counts in the blood and tissues of patients with sporotrichosis through automated blood analysis, histology, and immunohistochemistry. In addition, we found elevated granulocyte colony-stimulating factor levels by ELISAs. Flow cytometry analysis revealed a significant increase in CD16+CD66b+ LDNs compared with that in healthy controls. In vitro stimulation with Sporothrix globosa induced LDN generation. We observed positive correlations of LDN frequency with levels of CRP and myeloperoxidase. Conversely, granulocyte colony-stimulating factor levels were negatively correlated with LDN frequency. LDNs exhibited a combined mature/immature phenotype. Notably, transcriptomic analysis showed downregulation of pro-inflammatory signaling pathways in LDNs; functional assays also demonstrated reduced phagocytosis, ROS production, and neutrophil extracellular trap formation after stimulation with Sporothrix globosa. Degranulation did not exhibit significant changes, suggesting that LDNs constitute an impaired subpopulation. Our findings in the context of subcutaneous fungal infections indicate that LDN levels are significantly elevated in sporotrichosis and positively correlated with disease severity.
低密度中性粒细胞（LDNs）是外周血单个核细胞（PBMCs）中中性粒细胞的一个独特亚群。它们是全身感染的关键介质，可放大炎症反应，并可能影响疾病的严重程度和慢性病程。然而，它们在皮下真菌感染中的作用此前尚未得到研究。在本研究中，我们通过自动血液分析、组织学和免疫组织化学观察到孢子丝菌病患者血液和组织中的中性粒细胞计数增加。此外，我们通过酶联免疫吸附测定（ELISA）发现粒细胞集落刺激因子水平升高。流式细胞术分析显示，与健康对照相比，CD16+CD66b+ LDNs显著增加。用球形孢子丝菌进行体外刺激可诱导LDN生成。我们观察到LDN频率与C反应蛋白（CRP）和髓过氧化物酶水平呈正相关。相反，粒细胞集落刺激因子水平与LDN频率呈负相关。LDNs表现出成熟/未成熟的混合表型。值得注意的是，转录组分析显示LDNs中促炎信号通路下调；功能测定还表明，用球形孢子丝菌刺激后，吞噬作用、活性氧（ROS）产生和中性粒细胞胞外陷阱形成减少。脱颗粒未表现出显著变化，这表明LDNs构成了一个功能受损的亚群。我们在皮下真菌感染背景下的研究结果表明，孢子丝菌病中LDN水平显著升高，且与疾病严重程度呈正相关。
