Autophagy enhances NFκB activity in specific tissue macrophages by sequestering A20 to boost antifungal immunity.
Autophagy enhances NFκB activity in specific tissue macrophages by sequestering A20 to boost antifungal immunity.
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DOI：
10.1038/ncomms6779
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发表时间：
2015-01-22
影响因子：
16.6
通讯作者：
Shinohara, Mari L.
中科院分区：
文献类型：
--
作者：
Kanayama, Masashi;Inoue, Makoto;Danzaki, Keiko;Hammer, Gianna;He, You-Wen;Shinohara, Mari L.
免疫反应必须在稳定状态下得到很好的抑制，以避免过度炎症。然而，这些限制很快被移除以发挥抗微生物反应。在此，我们报道了自噬在早期宿主抗真菌反应中的作用，即通过A20螯合增强NFκB活性。NFκB活化的增强是通过自噬耗竭脾脏、腹膜和肾脏中F4/80 hi巨噬细胞中的NFκB抑制剂A20实现的。我们表明，p62，自噬适配蛋白，捕获A20隔离它在自噬体。这允许巨噬细胞释放趋化因子以募集中性粒细胞。事实上，由于中性粒细胞募集受损，骨髓细胞缺乏自噬的小鼠对白色念珠菌感染表现出更高的易感性。因此，至少在上述特定组织中，自噬似乎打破了F4/80 hi巨噬细胞中的A20依赖性抑制，F4/80 hi巨噬细胞表达丰富的A20并有助于启动有效的先天免疫应答。
Immune responses must be well restrained in a steady state to avoid excessive inflammation. However, such restraints are quickly removed to exert anti-microbial responses. Here, we report a role of autophagy in an early host anti-fungal response by enhancing NFκB activity through A20 sequestration. Enhancement of NFκB activation is achieved by autophagic depletion of A20, an NFκB inhibitor, in F4/80hi macrophages in the spleen, peritoneum, and kidney. We show that p62, an autophagic adaptor protein, captures A20 to sequester it in the autophagosome. This allows the macrophages to release chemokines to recruit neutrophils. Indeed, mice lacking autophagy in myeloid cells show higher susceptibility to Candida albicans infection due to impairment in neutrophil recruitment. Thus, at least in the specific aforementioned tissues, autophagy appears to break A20-dependent suppression in F4/80hi macrophages, which express abundant A20 and contribute to the initiation of efficient innate immune responses.
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影响因子：
6.7
作者：
Brothers KM;Gratacap RL;Barker SE;Newman ZR;Norum A;Wheeler RT
通讯作者：
Wheeler RT
影响因子：
13.3
作者：
Cemma, Marija;Kim, Peter Kijun;Brumell, John Hunter
通讯作者：
Brumell, John Hunter
影响因子：
56.9
作者：
Lee, EG;Boone, DL;Ma, A
通讯作者：
Ma, A
DOI：
10.1073/pnas.1210500109
发表时间：
2012-11-13
影响因子：
11.1
作者：
Castillo, Eliseo F.;Dekonenko, Alexander;Deretic, Vojo
通讯作者：
Deretic, Vojo
DOI：
10.1083/jcb.200412022
发表时间：
2005-05-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Komatsu M;Waguri S;Ueno T;Iwata J;Murata S;Tanida I;Ezaki J;Mizushima N;Ohsumi Y;Uchiyama Y;Kominami E;Tanaka K;Chiba T
通讯作者：
Chiba T