A spatially-organized multicellular innate immune response in lymph nodes limits systemic pathogen spread.
A spatially-organized multicellular innate immune response in lymph nodes limits systemic pathogen spread.
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DOI：
10.1016/j.cell.2012.07.021
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发表时间：
2012-09-14
期刊：
影响因子：
64.5
通讯作者：
Germain RN
中科院分区：
文献类型：
--
作者：
Kastenmüller W;Torabi-Parizi P;Subramanian N;Lämmermann T;Germain RN
将间质液和抗原转运至淋巴结的淋巴网络构成导管系统，除非在淋巴结本身中阻断传播，否则该导管系统可被入侵的病原体劫持以实现全身性传播。在这里，我们表明，不同的淋巴细胞（NK细胞，γ δ T细胞，NKT细胞和先天性CD8 + T细胞）的网络在空间上预先定位在淋巴窦衬里的哨兵巨噬细胞附近，在那里它们可以快速有效地接收炎性小体产生的IL-18和来自病原体感应吞噬细胞的额外细胞因子信号。这导致策略性定位的先天淋巴细胞快速分泌IFN γ，促进巨噬细胞群体中的抗微生物抗性。干扰这种先天性免疫反应回路允许淋巴传播细菌的全身传播。这些发现扩展了我们对淋巴结内细胞定位和局部细胞间通讯的功能意义的理解，同时强调了这些器官作为先天宿主防御的高度活跃位置的作用。
The lymphatic network that transports interstitial fluid and antigens to lymph nodes constitutes a conduit system that can be hijacked by invading pathogens to achieve systemic spread unless dissemination is blocked in the lymph node itself. Here we show that a network of diverse lymphoid cells (NK cells, γδ T cells, NKT cells, and innate-like CD8+ T cells) are spatially pre-positioned close to lymphatic sinus-lining sentinel macrophages where they can rapidly and efficiently receive inflammasome-generated IL-18 and additional cytokine signals from the pathogen-sensing phagocytes. This leads to rapid IFNγ secretion by the strategically positioned innate lymphocytes, fostering anti-microbial resistance in the macrophage population. Interference with this innate immune response loop allows systemic spread of lymph-borne bacteria. These findings extend our understanding of the functional significance of cellular positioning and local intercellular communication within lymph nodes, while emphasizing the role of these organs as highly active locations of innate host defense.
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感染期间淋巴结中中性粒细胞迁移的动态。
影响因子：
32.4
作者：
Chtanova, Tatyana;Schaeffer, Marie;Han, Seong-Ji;van Dooren, Giel G.;Nollmann, Marcelo;Herzmark, Paul;Chan, Shiao Wei;Satija, Harshita;Camfield, Kristin;Aaron, Holly;Striepen, Boris;Robey, Ellen A.
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3.8
作者：
Kettle, S;Alcami, A;Smith, GL
通讯作者：
Smith, GL
影响因子：
30.5
作者：
Kupz, Andreas;Guarda, Greta;Bedoui, Sammy
通讯作者：
Bedoui, Sammy
影响因子：
32.4
作者：
Bajenoff, Marc;Egen, Jackson G.;Germain, Ronald N.
通讯作者：
Germain, Ronald N.
影响因子：
56.9
作者：
DeGrendele, HC;Estess, P;Siegelman, MH
通讯作者：
Siegelman, MH