Jose S, Huber A, Kassam A, Weghorn K N, Powers-Fletcher M, Sharma D, Mukherjee A, Alder M N, Madan R
Division of Infectious Diseases, Department of Internal Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Infect Immun. 2026 Jan 7:e0022925. doi: 10.1128/iai.00229-25.
Neutrophils are dominant cells during acute immune response to infection (CDI). A higher number of infiltrating colonic neutrophils is clearly linked to greater tissue damage and severe CDI (3, 4). However, the mechanism(s) by which neutrophils exacerbate tissue damage in CDI remain unknown. We investigated the role of a neutrophil subset marked by Olfactomedin-4 expression (OLFM4 neutrophils) during CDI. Single-cell transcriptomics reveal that is increased in blood neutrophils of infected mice, and these cells exhibit gene signatures characterized by high expression of degranulation genes. In -infected mice, OLFM4 neutrophils aggregate to areas of severe intestinal epithelial cell (IEC) damage, and plasma OLFM4 was significantly increased in both -infected mice and patients. , OLFM4 neutrophils and recombinant OLFM4 protein exacerbated toxin-induced IEC damage. In sum, our studies provide novel insights into neutrophil-mediated pathology and highlight the role of OLFM4 neutrophils in worsening CDI-induced IEC damage.
中性粒细胞是感染性结肠炎（CDI）急性免疫反应中的主要细胞。浸润结肠的中性粒细胞数量增加显然与更严重的组织损伤和严重CDI相关（3,4）。然而，中性粒细胞在CDI中加剧组织损伤的机制尚不清楚。我们研究了以嗅觉介质4表达为特征的中性粒细胞亚群（OLFM4中性粒细胞）在CDI中的作用。单细胞转录组学显示，感染小鼠血液中的中性粒细胞中该细胞增加，并且这些细胞表现出以脱颗粒基因高表达为特征的基因特征。在感染的小鼠中，OLFM4中性粒细胞聚集到严重肠上皮细胞（IEC）损伤区域，并且在感染的小鼠和患者中血浆OLFM4均显著增加。此外，OLFM4中性粒细胞和重组OLFM4蛋白加剧了毒素诱导的IEC损伤。总之，我们的研究为中性粒细胞介导的病理学提供了新的见解，并突出了OLFM4中性粒细胞在加重CDI诱导的IEC损伤中的作用。
