IL-23-dependent IL-17 drives Th1-cell responses following Mycobacterium bovis BCG vaccination.
IL-23-dependent IL-17 drives Th1-cell responses following Mycobacterium bovis BCG vaccination.
复制标题
DOI：
10.1002/eji.201141569
复制
发表时间：
2012-02
影响因子：
5.4
通讯作者：
Khader, Shabaana A.
中科院分区：
文献类型：
--
作者：
Gopal, Radha;Lin, Yinyao;Obermajer, Natasa;Slight, Samantha;Nuthalapati, Nikhil;Ahmed, Mushtaq;Kalinski, Pawel;Khader, Shabaana A.
产生有效的T辅助细胞1型(Th1)反应是对抗细胞内细菌的免疫所必需的。然而，一些细胞内的细菌需要白介素17来驱动Th1免疫和随后的保护性宿主免疫。在牛分枝杆菌卡介苗(BCG)免疫小鼠的模型中，我们证明了依赖IL-17驱动Th1反应是克服细菌诱导的IL-10抑制效应的宿主机制。我们发现，卡介苗诱导的前列腺素E2(PGE2)促进IL-10的产生，而IL-10限制Th1反应，同时诱导IL-23和Th17分化。IL-17下调IL-10和诱导IL-12产生的能力允许产生后续的Th1反应。因此，在体内，卡介苗诱导的Th17应答先于Th1应答的产生，而IL-23途径的缺失降低了卡介苗诱导的Th17和Th1免疫以及随后疫苗诱导的对结核分枝杆菌攻击的保护作用。重要的是，在缺乏IL-10的情况下，卡介苗诱导的Th1反应以IL-17不依赖的方式发生。这些新的数据表明，IL-23/IL-17途径驱动Th1反应，特别是克服IL-10介导的抑制，并且在没有IL-10的情况下，BCG诱导的Th1免疫的产生不依赖于IL-17。
Generation of effective T helper cell type 1 (Th1) responses are required for immunity against intracellular bacteria. However, some intracellular bacteria require Interleukin (IL)-17 to drive Th1 immunity and subsequent protective host immunity. Here, in a model of Mycobacterium bovis Bacille Calmette Guerin (BCG) vaccination in mice, we demonstrate that the dependence on IL-17 to drive Th1 responses is a host mechanism to overcome bacteria-induced IL-10 inhibitory effects. We show that BCG-induced Prostaglandin-E2 (PGE2) promotes the production of IL-10 which limits Th1 responses, while simultaneously inducing IL-23 and Th17 differentiation. The ability of IL-17 to down-regulate IL-10 and induce IL-12 production allows the generation of subsequent Th1 responses. Accordingly, BCG-induced Th17 responses precedes generation of Th1 responses in vivo, while absence of IL-23 pathway decreases BCG vaccine-induced Th17 and Th1 immunity and subsequent vaccine-induced protection upon M.tuberculosis challenge. Importantly, in the absence of IL-10, BCG-induced Th1 responses occurs in an IL-17-independent manner. These novel data project the IL-23/IL-17 pathway in driving Th1 responses, specifically, to overcome IL-10 mediated inhibition and that in absence of IL-10, the generation of BCG induced Th1 immunity is IL-17-independent.
登录
查看更多内容
影响因子：
15.3
作者：
D'Andrea, A;Aste-Amezaga, M;Valiante, N M;Ma, X;Kubin, M;Trinchieri, G
通讯作者：
Trinchieri, G
影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
4.4
作者：
Ghilardi, N;Kljavin, N;de Sauvage, FJ
通讯作者：
de Sauvage, FJ
影响因子：
32.4
作者：
Oppmann, B;Lesley, R;Kastelein, RA
通讯作者：
Kastelein, RA
影响因子：
4.4
作者：
Cruz, Andrea;Khader, Shabaana A.;Castro, Antonio G.
通讯作者：
Castro, Antonio G.