Increased blood CD226^- inflammatory monocytes with low antigen presenting potential correlate positively with severity of hemorrhagic fever with renal syndrome

Hantaan virus (HTNV) infection can cause severe hemorrhagic fever with renal syndrome (HFRS). Inflammatory monocytes (iMOs) are involved in early antiviral responses. Previous studies have found that blood iMOs numbers increase in the acute phase of HFRS. Here, we further identified the phenotypic characteristics of iMOs in HFRS and explored whether phenotypic changes in iMOs were associated with HFRS severity. Blood samples from 85 HFRS patients were used for phenotypic analysis of iMOs by flow cytometry. Plasma HTNV load was determined using RT-PCR. THP-1 cells overexpressing CD226 were used to investigate the effects of CD226 on HLA-DR/DP/DQ and CD80 expression. A mouse model was used to test macrophage phenotype following HTNV infection. The proportion of CD226^- iMOs in the acute phase of HFRS was 66.83 (35.05-81.72) %, which was significantly higher than that in the convalescent phase (5.32 (1.36-13.52) %) and normal controls (7.39 (1.15-18.11) %) (<i>p</i> &lt; 0.0001). In the acute phase, the proportion of CD226^- iMOs increased more in patients with more severe HFRS and correlated positively with HTNV load and negatively with platelet count. Notably, CD226^- iMOs expressed lower levels of HLA-DR/DP/DQ and CD80 than CD226⁺ iMOs, and overexpression CD226 could enhance the expression of HLA-DR/DP/DQ and CD80. In a mouse model, HTNV also induced the expansion of CD226^- macrophages, with decreased expression of I-A/I-E and CD80. CD226^- iMOs increased during HTNV infection and the decrease in CD226 hampered the expression of HLA-DR/DP/DQ and CD80, which may promote the immune escape of HTNV and exacerbate clinical symptoms.

汉坦病毒（Hantaan virus, HTNV）感染可引发重型肾综合征出血热（hemorrhagic fever with renal syndrome, HFRS）。炎症性单核细胞（inflammatory monocytes, iMOs）参与早期抗病毒免疫应答。既往研究表明，肾综合征出血热急性期患者外周血iMOs数量升高。本研究进一步明确了HFRS患者iMOs的表型特征，并探讨iMOs表型改变与HFRS病情严重程度的相关性。研究纳入85例HFRS患者，采集其外周血样本，通过流式细胞术开展iMOs表型分析；采用RT-PCR检测血浆HTNV载量。构建过表达CD226的THP-1细胞系，以探究CD226对HLA-DR/DP/DQ及CD80表达的调控作用；同时利用小鼠模型验证HTNV感染后巨噬细胞的表型变化。肾综合征出血热急性期患者外周血CD226阴性（CD226⁻）iMOs占比为66.83（35.05~81.72）%，显著高于恢复期患者[5.32（1.36~13.52）%]及健康对照者[7.39（1.15~18.11）%]（p<0.0001）。急性期内，HFRS病情越严重的患者，其CD226⁻iMOs占比升高越显著，且该占比与HTNV载量呈正相关，与血小板计数呈负相关。值得注意的是，相较于CD226阳性（CD226⁺）iMOs，CD226⁻iMOs的HLA-DR/DP/DQ及CD80表达水平更低；过表达CD226则可上调这两种分子的表达。在小鼠模型中，HTNV感染同样可诱导CD226⁻巨噬细胞扩增，且其I-A/I-E及CD80表达水平降低。汉坦病毒感染过程中CD226⁻iMOs数量升高，而CD226表达下调会抑制HLA-DR/DP/DQ及CD80的表达，这可能促进HTNV的免疫逃逸并加重临床症状。

搜集汇总

背景与挑战

背景概述

该数据集基于一项医学研究，探讨了肾综合征出血热患者血液中CD226阴性炎症单核细胞的增加与疾病严重程度的关系。研究发现，在急性期，CD226阴性炎症单核细胞比例显著升高，且与汉坦病毒载量正相关、与血小板计数负相关，同时这些细胞表现出较低的抗原呈递能力，可能促进病毒免疫逃逸。研究通过流式细胞术、RT-PCR和小鼠模型验证了这些发现，为理解HFRS的免疫机制提供了新见解。