Myd88 Is Required for an Antibody Response to Retroviral Infection
Myd88 Is Required for an Antibody Response to Retroviral Infection
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DOI：
10.1371/journal.ppat.1000298
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发表时间：
2009-02-01
期刊：
影响因子：
6.7
通讯作者：
Littman, Dan R.
中科院分区：
文献类型：
--
作者：
Browne, Edward P.;Littman, Dan R.
尽管逆转录病毒已经被广泛研究了很多年，但关于免疫系统如何检测逆转录病毒感染以及产生免疫反应需要哪些先天途径的基本问题仍然没有答案。确定这些途径及其对抗逆转录病毒免疫反应的贡献将有助于开发针对艾滋病毒等逆转录病毒病原体的更有效的疫苗。我们研究了CD11c(+)树突状细胞(DC)和Toll样受体(TLR)信号通路在产生针对小鼠逆转录病毒病原体Friend鼠白血病病毒(F-MLV)的抗逆转录病毒免疫反应中所起的作用。F-MLV感染过程中树突状细胞的特异性缺失导致病毒滴度在感染后14天显著增加，表明树突状细胞在感染的免疫控制中的重要性。同样，MyD88基因敲除小鼠未能控制F-MLV，并在感染后的几个月内保持高病毒滴度(10(7)个病灶/脾)。值得注意的是，DC耗竭小鼠和MyD88基因敲除小鼠仅表现出CD8(+)T细胞反应的部分降低，而对F-MLV的抗体反应完全丧失。此外，被动地将免疫血清从野生型小鼠转移到MyD88基因敲除小鼠，挽救了F-MLV的控制。这些结果表明TLR信号和CD11c(+)树突状细胞在逆转录病毒的体液应答中起关键作用。
Although retroviruses have been extensively studied for many years, basic questions about how retroviral infections are detected by the immune system and which innate pathways are required for the generation of immune responses remain unanswered. Defining these pathways and how they contribute to the anti-retroviral immune responses would assist in the development of more effective vaccines for retroviral pathogens such as HIV. We have investigated the roles played by CD11c(+) dendritic cells ( DCs) and by Toll-like receptor (TLR) signaling pathways in the generation of an anti-retroviral immune response against a mouse retroviral pathogen, Friend murine leukemia virus (F-MLV). Specific deletion of DCs during F-MLV infection caused a significant increase in viral titers at 14 days post-infection, indicating the importance of DCs in immune control of the infection. Similarly, Myd88 knockout mice failed to control F-MLV, and sustained high viral titers (10(7) foci/spleen) for several months after infection. Strikingly, both DC-depleted mice and Myd88 knockout mice exhibited only a partial reduction of CD8(+) T cell responses, while the IgG antibody response to F-MLV was completely lost. Furthermore, passive transfer of immune serum from wild-type mice to Myd88 knockout mice rescued control of F-MLV. These results identify TLR signaling and CD11c(+) DCs as playing critical roles in the humoral response to retroviruses.