de Toledo Matheus Aparecido, de Lima João Victor Souza, Salomão Reinaldo, Leite Giuseppe G F
Division of Infectious Diseases, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo 04023-900, Brazil.
J Leukoc Biol. 2025 Apr 23;117(4). doi: 10.1093/jleuko/qiaf027.
Low-density neutrophils (LDNs) or polymorphonuclear myeloid-derived suppressor cells are involved in the pathogenesis of cancer, autoimmune, and infectious diseases. They are crucial in the host response to invading pathogens, especially during acute illness, and are associated with poor prognosis in many infectious diseases. However, their gene expression profile and contribution to disease outcomes are not well described. We conducted a meta-analysis of gene expression datasets from peripheral blood mononuclear cells (PBMCs), focusing on patients with viral and bacterial infections. We identified a consensus set of 2,798 differentially expressed genes. Among these, 49 genes were commonly found in both the neutrophil degranulation pathway and the granule lumen-specific community. To validate this signature, we evaluated its expression in RNA-seq datasets, finding consistent upregulation of 24 genes in severe infections, 17 of them overlapped with genes overexpressed in CD16int cells. We also investigated the abundance of LDN-related proteins in a PBMC proteomics dataset from a cohort of sepsis and septic shock patients. Out of the 17 genes analyzed, 13 corresponding proteins were identified, 10 of which demonstrated significantly higher abundance in sepsis and septic shock patients compared with healthy controls. In conclusion, our study identified a pattern of 17 upregulated LDN genes, common to PBMC transcriptome and RNA-seq, and upregulated in CD16int, associated with acute infections and severe clinical outcomes, marking the first time these genes have been collectively presented as a potential signature of LDNs in relation to disease severity. Further research with prospective cohorts is needed to validate this LDN signature and explore its clinical implications.
低密度中性粒细胞（LDNs）或多形核骨髓来源的抑制细胞参与癌症、自身免疫性疾病和感染性疾病的发病机制。它们在宿主对入侵病原体的反应中至关重要，尤其是在急性疾病期间，并且与许多感染性疾病的不良预后相关。然而，它们的基因表达谱及其对疾病结局的贡献尚未得到充分描述。我们对外周血单核细胞（PBMCs）的基因表达数据集进行了荟萃分析，重点关注病毒和细菌感染患者。我们确定了一组共2798个差异表达基因。其中，49个基因在中性粒细胞脱颗粒途径和颗粒腔特异性群落中均常见。为了验证这一特征，我们在RNA测序数据集中评估了其表达，发现在严重感染中24个基因一致上调，其中17个与CD16int细胞中过表达的基因重叠。我们还在一组脓毒症和脓毒性休克患者的PBMC蛋白质组学数据集中研究了LDN相关蛋白的丰度。在分析的17个基因中，鉴定出了13个相应的蛋白质，其中10个在脓毒症和脓毒性休克患者中的丰度明显高于健康对照。总之，我们的研究确定了17个上调的LDN基因模式，这在PBMC转录组和RNA测序中是常见的，并且在CD16int中上调，与急性感染和严重临床结局相关，这是首次将这些基因作为与疾病严重程度相关的LDN潜在特征进行集体呈现。需要对前瞻性队列进行进一步研究，以验证这一LDN特征并探索其临床意义。
