C5a regulates NKT and NK cell functions in sepsis.
C5a regulates NKT and NK cell functions in sepsis.
复制标题
DOI：
10.4049/jimmunol.1100338
复制
发表时间：
2011-12-01
期刊：
影响因子：
--
通讯作者：
Mattner J
中科院分区：
文献类型：
--
作者：
Fusakio ME;Mohammed JP;Laumonnier Y;Hoebe K;Köhl J;Mattner J
补体、自然杀伤T细胞(NKT)和自然杀伤细胞(NK)在抵抗病原体的第一线防御中起着至关重要的作用。两种C5a受体，即C5aR和C5L2在脓毒症中的功能作用已被证明。然而，C5a在脓毒症时先天淋巴细胞活化中的作用仍然不清楚。在这里，我们发现幼稚的NKT和NK细胞已经表达了高水平的C5aR和少量的C5L2 mRNA，但没有表达蛋白质。在大肠杆菌诱导的脓毒症中，我们发现C5aR在NKT和NK细胞亚群上表达，这表明在细菌接触时C5aR蛋白迅速转化为C5aR蛋白。重要的是，在没有C5aR、NKT和NK细胞的情况下，显著提高存活率，而不是C5L2，与降低干扰素-γ和肿瘤坏死因子-α水平有关。在C5aR+/C5aR−混合骨髓嵌合体诱导的脓毒症中，C5aR与NKT细胞的同源结合是NKT细胞募集的重要因素。此外，我们还发现C5aR和Toll样受体之间的协同作用增强了与DC共培养的NKT和NK细胞产生肿瘤坏死因子-α和干扰素-γ。我们的结果证实，C5aR激活是一种新的途径，在早期实验性脓毒症中驱动NKT和NK细胞的不利影响。
Complement, natural killer T (NKT) and natural killer (NK) cells play critical roles in the first line defense against pathogens. Functional roles for both C5a receptors, i.e. C5aR and C5L2 in sepsis have been demonstrated. However, the role of C5a in innate lymphocyte activation during sepsis remains elusive. Here, we show that naïve NKT and NK cells already express high levels of C5aR and minor levels of C5L2 mRNA, but no protein. Upon E. coli-induced sepsis, we found C5aR surface expression on subpopulations of NKT and NK cells suggesting rapid translation into C5aR protein upon bacterial encounter. Importantly, significantly increased survival in the absence of C5aR, NKT and NK cells, but not of C5L2, was associated with reduced IFN-γ and TNF-α serum levels. Sepsis induction in C5aR+/C5aR− mixed bone marrow chimeras identified cognate engagement of C5aR on NKT cells as an important factor for the recruitment of NKT cells. Further, we found synergistic interaction between C5aR and Toll-like receptors enhancing the production of TNF-α and IFN-γ from NKT and NK cells in co-cultures with DCs. Our results identify C5aR activation as a novel pathway driving detrimental effects of NKT and NK cells during early experimental sepsis.
登录
查看更多内容
DOI：
10.1084/jem.180.3.907
发表时间：
1994-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ozmen L;Pericin M;Hakimi J;Chizzonite RA;Wysocka M;Trinchieri G;Gately M;Garotta G
通讯作者：
Garotta G
影响因子：
4.4
作者：
Emoto, M;Miyamoto, M;Kaufmann, SHE
通讯作者：
Kaufmann, SHE
影响因子：
2.2
作者：
Liu, Yang;Goff, Randal D.;Savage, Paul B.
通讯作者：
Savage, Paul B.
影响因子：
32.4
作者：
Riedemann, NC;Guo, RF;Ward, PA
通讯作者：
Ward, PA
影响因子：
64.8
作者：
Mattner, J;DeBord, KL;Bendelac, A
通讯作者：
Bendelac, A