IFNAR1 信号在 NK 细胞中促进持续性病毒感染。

IFNAR1 signaling in NK cells promotes persistent virus infection.

机构信息

Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Department of Molecular Bioscience/Institute of Bioscience and Biotechnology, College of Biomedical Science, Kangwon National University, Chuncheon, Republic of Korea.

出版信息

Sci Adv. 2021 Mar 26;7(13). doi: 10.1126/sciadv.abb8087. Print 2021 Mar.

Inhibition of type 1 interferon (IFN-I) signaling promotes the control of persistent virus infection, but the underlying mechanisms remain poorly understood. Here, we report that genetic ablation of specifically in natural killer (NK) cells led to elevated numbers of T follicular helper cells, germinal center B cells, and plasma cells and improved antiviral T cell function, resulting in hastened virus clearance that was comparable to IFNAR1 neutralizing antibody treatment. Antigen-specific B cells and antiviral antibodies were essential for the accelerated control of LCMV Cl13 infection following IFNAR1 blockade. IFNAR1 signaling in NK cells promoted NK cell function and general killing of antigen-specific CD4 and CD8 T cells. Therefore, inhibition of IFN-I signaling in NK cells enhances CD4 and CD8 T cell responses, promotes humoral immune responses, and thereby facilitates the control of persistent virus infection.

抑制 I 型干扰素（IFN-I）信号转导可促进持续性病毒感染的控制，但其中的潜在机制仍知之甚少。在这里，我们报告说，特异性地在自然杀伤 (NK) 细胞中敲除导致滤泡辅助性 T 细胞、生发中心 B 细胞和浆细胞数量增加，并改善了抗病毒 T 细胞功能，从而加速了病毒清除，其效果可与 IFNAR1 中和抗体治疗相媲美。针对抗原的 B 细胞和抗病毒抗体对于在 IFNAR1 阻断后加速控制 LCMV Cl13 感染是必不可少的。NK 细胞中的 IFNAR1 信号转导促进了 NK 细胞功能和针对抗原特异性 CD4 和 CD8 T 细胞的一般杀伤。因此，抑制 NK 细胞中的 IFN-I 信号转导可增强 CD4 和 CD8 T 细胞的反应，促进体液免疫反应，从而有助于控制持续性病毒感染。