Differential ability of surface and endosomal TLRs to induce CD8 T cell responses in vivo.
Differential ability of surface and endosomal TLRs to induce CD8 T cell responses in vivo.
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DOI：
10.4049/jimmunol.1302244
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发表时间：
2014-05-01
期刊：
影响因子：
--
通讯作者：
Pasare C
中科院分区：
文献类型：
--
作者：
Mandraju R;Murray S;Forman J;Pasare C
树突状细胞（DC）上的Toll样受体（TLR）激活可诱导DC成熟以及促炎细胞因子的分泌，这两者对于CD4 T细胞的激活和分化都很重要。TLR在DC上的激活对CD8 T细胞反应的重要性则不太明确。在此，我们测试了不同的TLR调节CD8 T细胞对病原体反应的能力。我们发现，尽管所有的TLR都能在体外诱导CD8 T细胞激活，但它们在体内激活CD8 T细胞的能力存在显著差异。识别核酸的内体TLR（TLR3和TLR9）具有强大的诱导CD8 T细胞激活的能力。然而，识别细菌配体的表面TLR（TLR2和TLR4）不仅无法诱导CD8 T细胞的启动，而且对抑制由内体TLR激活所诱导的CD8 T细胞扩增具有主导作用。我们发现，TLR2和TLR4以一种依赖MyD88的方式，通过改变引流淋巴结中DC的组成来影响CD8 T细胞的启动。我们的结果对细菌和病毒混合感染具有重要意义，并表明细菌感染可能会限制宿主产生有效的抗病毒CD8 T细胞免疫的能力。
Toll Like Receptor (TLR) activation on dendritic cells (DCs) induces DC maturation and secretion of pro-inflammatory cytokines, both of which are important for activation and differentiation of CD4 T cells. The importance of TLR activation on DCs for CD8 T cell responses is less clear. Here, we tested the ability of different TLRs to regulate CD8 T cell responses to pathogens. We found that although all TLRs are able to induce CD8 T cell activation in vitro, there are profound differences in their ability to activate CD8 T cells in vivo. The nucleic acid recognizing endosomal TLRs, TLR3 and TLR9, had a potent ability to induce CD8 T cell activation. However, the surface TLRs, TLR2 and TLR4, that recognize bacterial ligands, were not only incapable of inducing CD8 T cell priming, but had a dominant effect of inhibiting CD8 T cell expansion induced by activation of endosomal TLRs. We found that TLR2 and TLR4, acting in a MyD88-dependent manner, influenced CD8 T cell priming by altering the composition of DCs in the draining lymph nodes. Our results have important implications for combined bacterial and viral infections and suggest that bacterial infections could constrain the ability of the host to mount effective anti-viral CD8 T cell immunity.
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影响因子：
30.5
作者：
Ackerman, AL;Kyritsis, C;Cresswell, P
通讯作者：
Cresswell, P
影响因子：
56.9
作者：
Blander, JM;Medzhitov, R
通讯作者：
Medzhitov, R
DOI：
10.1038/nri2569
发表时间：
2009-07
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Geijtenbeek TB;Gringhuis SI
通讯作者：
Gringhuis SI
影响因子：
32.4
作者：
Hu W;Troutman TD;Edukulla R;Pasare C
通讯作者：
Pasare C
影响因子：
7.7
作者：
Lee BL;Moon JE;Shu JH;Yuan L;Newman ZR;Schekman R;Barton GM
通讯作者：
Barton GM