Staphylococcus aureus uses the ArlRS and MgrA cascade to regulate immune evasion during skin infection.
Staphylococcus aureus uses the ArlRS and MgrA cascade to regulate immune evasion during skin infection.
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DOI：
10.1016/j.celrep.2021.109462
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发表时间：
2021-07-27
期刊：
影响因子：
8.8
通讯作者：
Horswill AR
中科院分区：
文献类型：
--
作者：
Kwiecinski JM;Kratofil RM;Parlet CP;Surewaard BGJ;Kubes P;Horswill AR
皮肤是机体对金黄色葡萄球菌感染产生免疫反应的最常见部位之一。在这里，通过体外试验，小鼠模型和活体成像的组合，我们发现，S。皮肤中的金黄色葡萄球菌免疫逃避由ArlRS双组分调节系统及其下游效应物MgrA组成的级联控制。S.缺乏ArlRS或MgrA的金黄色葡萄球菌的毒性较低，并且由于巨大表面蛋白Ebh的去抑制而不能形成正确的脓肿结构。这些S.金黄色葡萄球菌突变体还具有免疫逃避因子（杀白细胞素，S.金黄色葡萄球菌[CHIPS]、葡萄球菌补体抑制剂[SCIN]和核酸酶），并且不能杀死嗜中性粒细胞，阻断其趋化性，降解嗜中性粒细胞胞外陷阱，并在直接嗜中性粒细胞攻击中存活。脓肿结构的破坏和免疫逃避因子的减少使S.金黄色葡萄球菌易受宿主防御的影响因此，ArlRS和MgrA是S.金黄色葡萄球菌免疫逃避和有前途的治疗靶点。Kwiecinski等人表明，金黄色葡萄球菌在皮肤感染期间使用ArlRS-MgrA调节系统来协调基因表达。这种级联反应是正确的脓肿结构和宿主先天免疫系统的逃避所必需的，它们共同对完整的S。金黄色葡萄球菌毒力
Skin is one of the most common sites of host immune response against Staphylococcus aureus infection. Here, through a combination of in vitro assays, mouse models, and intravital imaging, we find that S. aureus immune evasion in skin is controlled by a cascade composed of the ArlRS two-component regulatory system and its downstream effector, MgrA. S. aureus lacking either ArlRS or MgrA is less virulent and unable to form correct abscess structure due to de-repression of a giant surface protein, Ebh. These S. aureus mutants also have decreased expression of immune evasion factors (leukocidins, chemotaxis-inhibitory protein of S. aureus [CHIPS], staphylococcal complement inhibitor [SCIN], and nuclease) and are unable to kill neutrophils, block their chemotaxis, degrade neutrophil extracellular traps, and survive direct neutrophil attack. The combination of disrupted abscess structure and reduced immune evasion factors makes S. aureus susceptible to host defenses. ArlRS and MgrA are therefore the main regulators of S. aureus immune evasion and promising treatment targets. Kwiecinski et al. show that Staphylococcus aureus uses the ArlRS-MgrA regulatory system to coordinate gene expression during skin infection. This cascade is required for proper abscess structuring and evasion of the host innate immune system, which together are essential for full S. aureus virulence.
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