Deficiency of the B Cell-Activating Factor Receptor Results in Limited CD169+ Macrophage Function during Viral Infection
Deficiency of the B Cell-Activating Factor Receptor Results in Limited CD169+ Macrophage Function during Viral Infection
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B 细胞激活因子受体缺陷导致病毒感染期间 CD169 巨噬细胞功能有限
DOI：
10.1128/jvi.02976-14
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发表时间：
2015
影响因子：
5.4
通讯作者：
Lang KS
中科院分区：
文献类型：
--
作者：
Huang J;Khairnar V;Duhan V;Pandyra AA;Grusdat M;Shinde P;McIlwain DR;Maney SK;Gommerman J;Löhning M;Ohashi PS;Mak TW;Pieper K;Speletas M;Eibel H;Ware CF;Tumanov AV;Kruglov AA;Nedospasov SA;Häusinger D;Recher M;Lang KS
B细胞活化因子（BAFF）对小鼠和人类的B细胞发育和体液免疫至关重要。虽然BAFF在B细胞中的作用已被广泛描述，但其在先天免疫中的作用仍不清楚。使用BAFF受体（BAFFR）缺陷小鼠，我们的特点BAFFR相关的先天性和适应性免疫功能感染水泡性口炎病毒（VSV）和淋巴细胞性脉络丛脑膜炎病毒（LCMV）。我们确定了BAFFR信号传导在CD 169+巨噬细胞区室的产生和维持中的关键作用。因此，Baffr−/−小鼠在病毒感染后表现出有限的先天I型干扰素产生诱导。BAFFR信号传导的缺乏减少了病毒感染后的病毒扩增和呈递，导致抗病毒适应性免疫应答的高度降低。因此，BAFFR缺陷小鼠在病毒感染后表现出恶化和致命的疾病。从机制上讲，Baffr −/−动物中B细胞的短暂缺乏导致了有限的CD 169+细胞表达，这对维持CD 169+细胞至关重要。总之，BAFFR信号在病毒感染期间影响先天性和适应性免疫激活。重要信息病毒引起人类急性和慢性感染，每年导致数百万人死亡。先天免疫对于病毒感染的结果至关重要。先天性I型干扰素的产生可以限制病毒复制，而先天免疫细胞的适应性免疫引发诱导病原体特异性免疫并具有长期保护作用。在这里，我们表明，BAFFR缺乏不仅扰乱B细胞，但也导致有限的CD 169+巨噬细胞。这些巨噬细胞在扩增病毒颗粒以触发I型干扰素产生和启动适应性免疫引发中至关重要。因此，BAFFR缺陷导致减少强制病毒复制，有限的I型干扰素的生产，并减少适应性免疫力相比，BAFFR的能力控制。因此，BAFFR缺陷小鼠易受致命性病毒感染。因此，BAFFR表达对于先天免疫激活和抗病毒免疫是至关重要的。
The B cell-activating factor (BAFF) is critical for B cell development and humoral immunity in mice and humans. While the role of BAFF in B cells has been widely described, its role in innate immunity remains unknown. Using BAFF receptor (BAFFR)-deficient mice, we characterized BAFFR-related innate and adaptive immune functions following infection with vesicular stomatitis virus (VSV) and lymphocytic choriomeningitis virus (LCMV). We identified a critical role for BAFFR signaling in the generation and maintenance of the CD169+macrophage compartment. Consequently,Baffr−/−mice exhibited limited induction of innate type I interferon production after viral infection. Lack of BAFFR signaling reduced virus amplification and presentation following viral infection, resulting in highly reduced antiviral adaptive immune responses. As a consequence, BAFFR-deficient mice showed exacerbated and fatal disease after viral infection. Mechanistically, transient lack of B cells inBaffr−/−animals resulted in limited lymphotoxin expression, which is critical for maintenance of CD169+cells. In conclusion, BAFFR signaling affects both innate and adaptive immune activation during viral infections.IMPORTANCEViruses cause acute and chronic infections in humans resulting in millions of deaths every year. Innate immunity is critical for the outcome of a viral infection. Innate type I interferon production can limit viral replication, while adaptive immune priming by innate immune cells induces pathogen-specific immunity with long-term protection. Here, we show that BAFFR deficiency not only perturbed B cells, but also resulted in limited CD169+macrophages. These macrophages are critical in amplifying viral particles to trigger type I interferon production and initiate adaptive immune priming. Consequently, BAFFR deficiency resulted in reduced enforced viral replication, limited type I interferon production, and reduced adaptive immunity compared to BAFFR-competent controls. As a result, BAFFR-deficient mice were predisposed to fatal viral infections. Thus, BAFFR expression is critical for innate immune activation and antiviral immunity.
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影响因子：
15.9
作者：
McCarthy, Douglas D.;Kujawa, Julie;Browning, Jeffrey L.
通讯作者：
Browning, Jeffrey L.
影响因子：
6.7
作者：
Honke N;Shaabani N;Zhang DE;Iliakis G;Xu HC;Häussinger D;Recher M;Löhning M;Lang PA;Lang KS
通讯作者：
Lang KS
影响因子：
12.4
作者：
通讯作者：
--
抗原的定位剂量和时间决定免疫反应性。
影响因子：
7.8
作者：
R. Zinkernagel
通讯作者：
R. Zinkernagel
影响因子：
32.4
作者：
Tumanov, AV;Kuprash, DV;Nedospasov, SA
通讯作者：
Nedospasov, SA