Macrophage Death following Influenza Vaccination Initiates the Inflammatory Response that Promotes Dendritic Cell Function in the Draining Lymph Node
Macrophage Death following Influenza Vaccination Initiates the Inflammatory Response that Promotes Dendritic Cell Function in the Draining Lymph Node
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DOI：
10.1016/j.celrep.2017.02.026
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发表时间：
2017-03-07
期刊：
影响因子：
8.8
通讯作者：
Gonzalez, Santiago F.
中科院分区：
文献类型：
--
作者：
Chatziandreou, Nikolaos;Farsakoglu, Yagmur;Gonzalez, Santiago F.
炎症影响对疫苗的适应性反应的机制尚未完全了解。在这里，我们研究了淋巴结巨噬细胞（LNM）在诱导灭活流感病毒疫苗引发的细胞因子风暴中的作用。接种疫苗后，LNM经历炎性小体非依赖性坏死样死亡，其依赖于MyD 88和Toll样受体7（TLR 7）表达并释放预储存的白细胞介素-la（IL-la）。此外，活化的髓质巨噬细胞产生干扰素-b（IFN-b），其诱导IL-1a的自分泌分泌。我们还发现，巨噬细胞耗竭促进淋巴结驻留树突状细胞（LNDC）的重新定位，并影响CD 11b（+）LNDC捕获病毒和表达共刺激分子的能力。抑制IL-1 a诱导的炎症级联反应降低了B细胞应答，而同时给予重组IL-1 a增加了体液应答。因此，IL-1a炎症通路的刺激可能代表了增强LNDC的抗原呈递和改善针对流感疫苗的体液应答的策略。
The mechanism by which inflammation influences the adaptive response to vaccines is not fully understood. Here, we examine the role of lymph node macrophages (LNMs) in the induction of the cytokine storm triggered by inactivated influenza virus vaccine. Following vaccination, LNMs undergo inflammasome- independent necrosis-like death that is reliant on MyD88 and Toll-like receptor 7 (TLR7) expression and releases pre-stored interleukin-1a (IL-1a). Furthermore, activated medullary macrophages produce interferon-b (IFN-b) that induces the autocrine secretion of IL-1a. We also found that macrophage depletion promotes lymph node-resident dendritic cell (LNDC) relocation and affects the capacity of CD11b(+) LNDCs to capture virus and express co-stimulatory molecules. Inhibition of the IL-1a-induced inflammatory cascade reduced B cell responses, while co-administration of recombinant IL-1a increased the humoral response. Stimulation of the IL-1a inflammatory pathway might therefore represent a strategy to enhance antigen presentation by LNDCs and improve the humoral response against influenza vaccines.