The cysteine protease ApdS from Streptococcus suis promotes evasion of innate immune defenses by cleaving the antimicrobial peptide cathelicidin LL-37
The cysteine protease ApdS from Streptococcus suis promotes evasion of innate immune defenses by cleaving the antimicrobial peptide cathelicidin LL-37
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来自猪链球菌的半胱氨酸蛋白酶 ApdS 通过裂解抗菌肽抗菌肽 LL-37 促进先天免疫防御的逃避
DOI：
10.1074/jbc.ra119.009441
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发表时间：
2019-10
影响因子：
4.8
通讯作者：
Siguo Liu
中科院分区：
文献类型：
--
作者：
Fang Xie;Yanan Zan;Yueling Zhang;Ning Zheng;Qiulong Yan;Wanjiang Zhang;Huihui Zhang;Mingjie Jin;Fuguang Chen;Xinyuan Zhang;Siguo Liu
猪链球菌是一种全球性分布的人畜共患病原体，可引起人类脑膜炎和败血症，对公众健康构成严重威胁。为了在宿主体内成功入侵和传播，这种细菌必须克服先天免疫系统。抗菌肽LL-37通过直接穿透细菌膜和刺激中性粒细胞的免疫功能来阻止入侵病原体，中性粒细胞是抗S.猪。然而，对S.猪和LL-37以及这种细菌如何适应和逃避LL-37介导的免疫应答。本研究通过酶法、趋化性、细胞因子测定、定量RT-PCR和CD光谱等方法，发现S. suis切割LL-37，从而在S.猪和人嗜中性粒细胞。S.猪链球菌感染刺激人中性粒细胞产生LL-37;猪暴露于LL-37上调细菌中ApdS蛋白酶的表达。我们观察到ApdS靶向并快速切割LL-37，削弱其对S的杀菌活性。猪。我们将这种效应归因于截短肽中二级结构的螺旋含量降低。此外，ApdS拯救了S。由于LL-37截短减弱了嗜中性粒细胞的趋化性，抑制了细胞外陷阱的形成和活性氧的产生，总之，我们的研究结果揭示了免疫抑制策略的S。suis，由此细菌通过ApdS蛋白酶介导的LL-37切割削弱先天宿主防御。
Streptococcus suis is a globally distributed zoonotic pathogen associated with meningitis and septicemia in humans, posing a serious threat to public health. To successfully invade and disseminate within its host, this bacterium must overcome the innate immune system. The antimicrobial peptide LL-37 impedes invading pathogens by directly perforating bacterial membranes and stimulating the immune function of neutrophils, which are the major effector cells against S. suis. However, little is known about the biological relationship between S. suis and LL-37 and how this bacterium adapts to and evades LL-37–mediated immune responses. In this study by using an array of approaches, including enzyme, chemotaxis, cytokine assays, quantitative RT-PCR, and CD spectroscopy, we found that the cysteine protease ApdS from S. suis cleaves LL-37 and thereby plays a key role in the interaction between S. suis and human neutrophils. S. suis infection stimulated LL-37 production in human neutrophils, and S. suis exposure to LL-37 up-regulated ApdS protease expression in the bacterium. We observed that ApdS targets and rapidly cleaves LL-37, impairing its bactericidal activity against S. suis. We attributed this effect to the decreased helical content of the secondary structure in the truncated peptide. Moreover, ApdS rescued S. suis from killing by human neutrophils and neutrophil extracellular traps because LL-37 truncation attenuated neutrophil chemotaxis and inhibited the formation of extracellular traps and the production of reactive oxygen species. Altogether, our findings reveal an immunosuppressive strategy of S. suis whereby the bacterium blunts the innate host defenses via ApdS protease-mediated LL-37 cleavage.
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影响因子：
14.9
作者：
Micsonai A;Wien F;Bulyáki É;Kun J;Moussong É;Lee YH;Goto Y;Réfrégiers M;Kardos J
通讯作者：
Kardos J
影响因子：
20.3
作者：
O. Sørensen;K. Arnljots;J. Cowland;D. Bainton;N. Borregaard
通讯作者：
O. Sørensen;K. Arnljots;J. Cowland;D. Bainton;N. Borregaard
影响因子：
4.4
作者：
Tang, Xiao;Basavarajappa, Devaraj;Wan, Min
通讯作者：
Wan, Min
影响因子：
2.1
作者：
Okwumabua, O;O'Connor, M;Shull, E
通讯作者：
Shull, E
DOI：
10.1016/j.jcf.2003.12.008
发表时间：
2004-03-01
期刊：
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society
影响因子：
--
作者：
Chen, Christiane I-U;Schaller-Bals, Susanne;Bals, Robert
通讯作者：
Bals, Robert