Department of Microbiology and Immunology, Shanghai Jiao Tong University School of Medicine.
Shanghai Immune Therapy Institute, Renji Hospital and Baoshan Branch of Renji Hospital, Shanghai Jiao Tong University School of Medicine.
J Infect Dis. 2024 Jul 25;230(1):5-14. doi: 10.1093/infdis/jiae048.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a variety of clinical manifestations, many of which originate from altered immune responses, either locally or systemically. Immune cell cross-talk occurs mainly in lymphoid organs. However, systemic cell interaction specific to coronavirus disease 2019 has not been well characterized. Here, by employing single-cell RNA sequencing and imaging flow cytometry analysis, we unraveled, in peripheral blood, a heterogeneous group of cell complexes formed by the adherence of CD14+ monocytes to different cytotoxic lymphocytes, including SARS-CoV-2-specific CD8+ T cells, γδ T cells, and natural killer T cells. These lymphocytes attached to CD14+ monocytes that showed enhanced inflammasome activation and pyroptosis-induced cell death in progression stage; in contrast, in the convalescent phase, CD14+ monocytes with elevated antigen presentation potential were targeted by cytotoxic lymphocytes, thereby restricting the excessive immune activation. Collectively, our study reports previously unrecognized cell-cell interplay in the SARS-CoV-2-specific immune response, providing new insight into the intricacy of dynamic immune cell interaction representing antiviral defense.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染引起多种临床表现，其中许多源自局部或全身免疫反应的改变。免疫细胞相互作用主要发生在淋巴器官中。然而，针对 2019 年冠状病毒病的全身细胞相互作用尚未得到很好的描述。在这里，通过单细胞 RNA 测序和成像流式细胞术分析，我们在血液中揭示了一组由 CD14+单核细胞与不同细胞毒性淋巴细胞（包括 SARS-CoV-2 特异性 CD8+T 细胞、γδ T 细胞和自然杀伤 T 细胞）附着形成的异质细胞复合物。这些淋巴细胞附着在 CD14+单核细胞上，在进展阶段表现出增强的炎症小体激活和细胞焦亡诱导的细胞死亡；相比之下，在恢复期，具有增强抗原呈递潜力的 CD14+单核细胞被细胞毒性淋巴细胞靶向，从而限制了过度的免疫激活。总的来说，我们的研究报告了 SARS-CoV-2 特异性免疫反应中以前未被识别的细胞-细胞相互作用，为代表抗病毒防御的动态免疫细胞相互作用的复杂性提供了新的见解。
