Lymph node but not intradermal injection site macrophages are critical for germinal center formation and antibody responses to rabies vaccination.
Lymph node but not intradermal injection site macrophages are critical for germinal center formation and antibody responses to rabies vaccination.
复制标题
淋巴结而非皮内注射部位的巨噬细胞对于生发中心的形成和狂犬病疫苗接种的抗体反应至关重要。
DOI：
10.1128/jvi.03409-14
复制
发表时间：
2015
影响因子：
5.4
通讯作者：
McGettigan,JamesP
中科院分区：
文献类型：
--
作者：
Lytle,AndrewG;Shen,Shixue;McGettigan,JamesP
基于复制缺陷狂犬病毒（RABV）的疫苗通过T细胞非依赖性和T细胞依赖性机制诱导快速有效的抗体反应。为了进一步研究疫苗诱导的抗RABV感染抗体应答的早期事件，我们研究了巨噬细胞作为RABV疫苗免疫原性介质的作用。在这篇报道中，我们展示了一种重组基质基因缺失的rabv疫苗（rRABV-ΔM）在体外感染并激活原代小鼠巨噬蛋白。用rabv活疫苗免疫小鼠可导致巨噬细胞在免疫部位聚集，这表明组织中的巨噬细胞支持有效的抗rabv B细胞反应的发展。然而，我们发现引流淋巴结巨噬细胞，而不是免疫部位的巨噬细胞，对生发中心B细胞、滤泡T辅助细胞和rabv特异性抗体的产生至关重要。我们的研究结果对基于RABV的新型疫苗的设计具有启示意义，因为早期免疫事件对于暴露后环境中对RABV的保护是重要的。重要意义超过三分之二的世界人口生活在狂犬病流行地区。接触后预防是治疗人类的主要手段。确定指导开发针对狂犬病感染的快速和有效抗体反应的免疫学原理将大大提高我们生产更有效的狂犬病疫苗的能力。在这里，我们报告了淋巴引流淋巴结中的巨噬细胞，而不是免疫部位的组织中的巨噬细胞对疫苗诱导的狂犬病抗体反应很重要。从这项研究中收集的信息可能有助于指导针对狂犬病感染的单剂量疫苗的开发。
Replication-deficient rabies virus (RABV)-based vaccines induce rapid and potent antibody responses via T cell-independent and T cell-dependent mechanisms. To further investigate early events in vaccine-induced antibody responses against RABV infections, we studied the role of macrophages as mediators of RABV-based vaccine immunogenicity. In this report, we show that a recombinant matrix gene-deleted RABV-based vaccine (rRABV-ΔM) infects and activates primary murine macrophagesin vitro. Immunization of mice with live RABV-based vaccines results in accumulation of macrophages at the site of immunization, which suggests that macrophages in tissues support the development of effective anti-RABV B cell responses. However, we show that draining lymph node macrophages, but not macrophages at the site of immunization, are essential for the generation of germinal center B cells, follicular T helper cells, and RABV-specific antibodies. Our findings have implications for the design of new RABV-based vaccines for which early immunological events are important for the protection against RABV in postexposure settings.IMPORTANCEMore than two-thirds of the world's population live in regions where rabies is endemic. Postexposure prophylaxis is the primary means of treating humans. Identifying immunological principles that guide the development of rapid and potent antibody responses against rabies infections will greatly increase our ability to produce more-effective rabies vaccines. Here we report that macrophages in the draining lymph node, but not in the tissue at the site of immunization are important for vaccine-induced antibody responses to rabies. Information gleaned from this study may help guide the development of a single-dose vaccine against rabies infections.