Staphylococcus aureus leukotoxin ED targets the chemokine receptors CXCR1 and CXCR2 to kill leukocytes and promote infection.
Staphylococcus aureus leukotoxin ED targets the chemokine receptors CXCR1 and CXCR2 to kill leukocytes and promote infection.
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DOI：
10.1016/j.chom.2013.09.005
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发表时间：
2013-10-16
影响因子：
30.3
通讯作者：
Torres VJ
中科院分区：
文献类型：
--
作者：
Reyes-Robles T;Alonzo F 3rd;Kozhaya L;Lacy DB;Unutmaz D;Torres VJ
金黄色葡萄球菌白细胞毒素艾德（Luk艾德）是小鼠模型中与菌血症相关的致死性所需的成孔毒素。LukED靶向趋化因子受体CCR 5以杀死T淋巴细胞、巨噬细胞和树突状细胞。LukED还杀死CCR 5缺陷细胞，如中性粒细胞，表明存在额外的细胞受体。在这里，我们确定趋化因子受体CXCR 1和CXCR 2作为中性粒细胞上LukED的靶点。LukE亚基以特异性和可饱和的方式结合中性粒细胞，这种相互作用被CXCL 8抑制，CXCL 8是CXCR 1和CXCR 2的高亲和力内源性配体。LukED识别CXCR 1和CXCR 2促进体外杀伤单核细胞和中性粒细胞。LukED介导的CXCR 1/CXCR 2+细胞靶向有助于S.金黄色葡萄球菌的发病机制，并促进致死性全身感染的小鼠。因此，LukED是一种多功能毒素，赋予S。金黄色葡萄球菌具有同时解除宿主免疫应答的先天性和适应性区室的能力。
The Staphylococcus aureus leukotoxin ED (LukED) is a pore-forming toxin required for the lethality associated with bacteremia in murine models. LukED targets the chemokine receptor CCR5 to kill T lymphocytes, macrophages and dendritic cells. LukED also kills CCR5-deficient cells like neutrophils, suggesting the existence of additional cellular receptors. Here we identify the chemokine receptors CXCR1 and CXCR2 as the targets of LukED on neutrophils. The LukE subunit binds neutrophils in a specific and saturable manner and this interaction is inhibited by CXCL8, the high affinity endogenous ligand of CXCR1 and CXCR2. LukED recognition of CXCR1 and CXCR2 promotes the killing of monocytes and neutrophils in vitro. LukED-mediated targeting of CXCR1/CXCR2+ cells contributes to S. aureus pathogenesis and facilitates lethality in systemically infected mice. Thus, LukED is a versatile toxin that endows S. aureus with the ability to simultaneously disarm both innate and adaptive compartments of the host immune response.
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影响因子：
3.6
作者：
Alonzo F 3rd;Benson MA;Chen J;Novick RP;Shopsin B;Torres VJ
通讯作者：
Torres VJ
影响因子：
30.3
作者：
Spaan, Andras N.;Henry, Thomas;van Strijp, Jos A. G.
通讯作者：
van Strijp, Jos A. G.
影响因子：
6.7
作者：
Lin L;Ibrahim AS;Xu X;Farber JM;Avanesian V;Baquir B;Fu Y;French SW;Edwards JE Jr;Spellberg B
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Spellberg B
影响因子：
56.9
作者：
Corbin, Brian D.;Seeley, Erin H.;Skaar, Eric P.
通讯作者：
Skaar, Eric P.
影响因子：
64.5
作者：
Liu, R;Paxton, WA;Landau, NR
通讯作者：
Landau, NR