Sheneman Katelyn R, Cummins Timothy D, Merchant Michael L, Hood Joshua L, Uriarte Silvia M, Lawrenz Matthew B
Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA.
Department of Medicine and Proteomics Technology Center, University of Louisville, Louisville, Kentucky, USA.
J Extracell Vesicles. 2025 Apr;14(4):e70074. doi: 10.1002/jev2.70074.
Yersinia pestis is the etiologic agent of the plague. A hallmark of plague is subversion of the host immune response by disrupting host signalling pathways required for inflammation. This non-inflammatory environment permits bacterial colonization and has been shown to be essential for disease manifestation. Previous work has shown that Y. pestis inhibits phagocytosis and degranulation by neutrophils. Manipulation of these key vesicular trafficking pathways suggests that Y. pestis influences extracellular vesicle (EV) secretion, cargo selection, trafficking and/or maturation. Our goals were to define the EV population produced by neutrophils in response to Y. pestis and determine how these vesicles might influence inflammation. Towards these goals, EVs were isolated from human neutrophils infected with Y. pestis or a mutant lacking bacterial effector proteins known to manipulate host cell signalling. Mass spectrometry data revealed that cargoes packaged in EVs isolated from mutant infected cells were enriched with antimicrobial and cytotoxic proteins, contents which differed from uninfected and Y. pestis infected cells. Further, EVs produced in response to Y. pestis lacked inflammatory properties observed in those isolated from neutrophils responding to the mutant. Together, these data demonstrate that Y. pestis actively inhibits the production of antimicrobial EVs produced by neutrophils, likely contributing to immune evasion.
鼠疫耶尔森菌是鼠疫的病原体。鼠疫的一个标志是通过破坏炎症所需的宿主信号通路来颠覆宿主免疫反应。这种非炎症环境允许细菌定植，并且已被证明对疾病表现至关重要。先前的研究表明，鼠疫耶尔森菌可抑制中性粒细胞的吞噬作用和脱颗粒。对这些关键囊泡运输途径的操控表明，鼠疫耶尔森菌会影响细胞外囊泡（EV）的分泌、货物选择、运输和/或成熟。我们的目标是确定中性粒细胞在响应鼠疫耶尔森菌时产生的EV群体，并确定这些囊泡如何影响炎症。为了实现这些目标，从感染了鼠疫耶尔森菌或缺乏已知可操控宿主细胞信号的细菌效应蛋白的突变体的人类中性粒细胞中分离出EV。质谱数据显示，从感染突变体的细胞中分离出的EV中包装的货物富含抗菌和细胞毒性蛋白，这些成分与未感染和感染鼠疫耶尔森菌的细胞不同。此外，响应鼠疫耶尔森菌产生的EV缺乏在从响应突变体的中性粒细胞中分离出的EV中观察到的炎症特性。总之，这些数据表明，鼠疫耶尔森菌会积极抑制中性粒细胞产生的抗菌EV的产生，这可能有助于免疫逃避。
