Systemic and mucosal mobilization of granulocyte subsets during lentiviral infection.
Systemic and mucosal mobilization of granulocyte subsets during lentiviral infection.
复制标题
慢病毒感染期间粒细胞亚群的全身和粘膜动员。
DOI：
10.1111/imm.13376
复制
发表时间：
2021
期刊：
影响因子：
6.4
通讯作者：
Reeves,RKeith
中科院分区：
文献类型：
--
作者：
Jones,Rhianna;Manickam,Cordelia;Ram,DanielR;Kroll,Kyle;Hueber,Brady;Woolley,Griffin;Shah,SpandanV;Smith,Scott;Varner,Valerie;Reeves,RKeith
粒细胞通过吞噬、细胞外陷阱、释放细胞毒颗粒、抗体效应器功能和其他免疫细胞对病原体的募集来介导广泛的免疫保护。然而，对HIV感染和粘膜组织中粒细胞的描述有限。我们的目标是利用恒河猴(RM)模型研究慢病毒感染期间全身、粘膜和淋巴组织中粒细胞亚群的特征。用显微镜和多色流式细胞术分析了实验幼稚和慢性SHIVsf162p3感染的RM空肠、结肠、宫颈、阴道、淋巴结、脾、肝和全血中的单个核细胞。粒细胞的鉴定使用专为RM设计的表型：嗜酸性粒细胞-CD45+CD66+CD49d+；中性粒细胞-CD45+CD66+CD14+；以及嗜碱性粒细胞-CD45+CD123+FCRε+。DAPI染色的核可视化和ImageStream(细胞仪/显微镜)的表面标记图像进一步证实了粒细胞的表型。流式细胞仪检测结果显示，所有RM粒细胞均表达CD32(FcrγII)，但不表达CD16(FcrγIII)。此外，中性粒细胞上CD6 4(FcRγI)和嗜碱性粒细胞上Fcrε的组成性表达表明，Fc受体在粒细胞亚群上的表达存在差异。幼稚全血粒细胞亚群中性粒细胞占25.4%~81.5%，嗜酸性粒细胞占0.059%~13.3%，嗜碱性粒细胞占0.059%~1.8%。有趣的是，在慢性慢病毒病中，循环中的中性粒细胞、大肠中性粒细胞和大肠嗜酸性粒细胞的频率都升高了。相反，SHIVsf162p3感染的RM循环中的嗜碱性粒细胞、空肠嗜酸性粒细胞、阴道中性粒细胞和阴道嗜酸性粒细胞减少。总体而言，我们的数据表明慢性慢病毒感染中粒细胞的调节，最明显的是在胃肠道粘膜，慢病毒诱导的疾病中发生显著的炎症和破坏。此外，在感染过程中，粒细胞可能会迁移到炎症组织，并可能成为免疫治疗干预的靶点。
Granulocytes mediate broad immunoprotection through phagocytosis, extracellular traps, release of cytotoxic granules, antibody effector functions and recruitment of other immune cells against pathogens. However, descriptions of granulocytes in HIV infection and mucosal tissues are limited. Our goal was to characterize granulocyte subsets in systemic, mucosal and lymphoid tissues during lentiviral infection using the rhesus macaque (RM) model. Mononuclear cells from jejunum, colon, cervix, vagina, lymph nodes, spleen, liver and whole blood from experimentally naïve and chronically SHIVsf162p3‐infected RM were analysed by microscopy and polychromatic flow cytometry. Granulocytes were identified using phenotypes designed specifically for RM: eosinophils—CD45+CD66+CD49d+; neutrophils—CD45+CD66+CD14+; and basophils—CD45+CD123+FcRε+. Nuclear visualization with DAPI staining and surface marker images by ImageStream (cytometry/microscopy) further confirmed granulocytic phenotypes. Flow cytometric data showed that all RM granulocytes expressed CD32 (FcRγII) but did not express CD16 (FcRγIII). Additionally, constitutive expression of CD64 (FcRγI) on neutrophils and FcRε on basophils indicates the differential expression of Fc receptors on granulocyte subsets. Granulocytic subsets in naïve whole blood ranged from 25·4% to 81·5% neutrophils, 0·59% to 13·3% eosinophils and 0·059% to 1·8% basophils. Interestingly, elevated frequencies of circulating neutrophils, colorectal neutrophils and colorectal eosinophils were all observed in chronic lentiviral disease. Conversely, circulating basophils, jejunal eosinophils, vaginal neutrophils and vaginal eosinophils of SHIVsf162p3‐infected RM declined in frequency. Overall, our data suggest modulation of granulocytes in chronic lentiviral infection, most notably in the gastrointestinal mucosae where a significant inflammation and disruption occurs in lentivirus‐induced disease. Furthermore, granulocytes may migrate to inflamed tissues during infection and could serve as targets of immunotherapeutic intervention.