Tissue-specific patterning of host innate immune responses by Staphylococcus aureus α-toxin.
Tissue-specific patterning of host innate immune responses by Staphylococcus aureus α-toxin.
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DOI：
10.1159/000360006
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发表时间：
2014
影响因子：
5.3
通讯作者：
Bubeck Wardenburg J
中科院分区：
文献类型：
--
作者：
Becker RE;Berube BJ;Sampedro GR;DeDent AC;Bubeck Wardenburg J
免疫调节性细胞毒素是由金黄色葡萄球菌产生的主要毒力因子，是细菌性败血症、皮肤感染和肺炎的主要原因。S.金黄色葡萄球菌α毒素是一种致孔毒素，它利用广泛表达的受体ADAM 10损伤宿主上皮、内皮和免疫细胞。由于每种宿主组织的特征在于驻留细胞和募集的免疫细胞的独特组成，因此α-毒素介导的损伤的结果可能取决于感染的组织环境。利用髓系特异性Adam 10基因敲除小鼠，我们发现α毒素对葡萄球菌感染的先天免疫产生组织特异性作用。ADAM 10表达的缺失加剧了皮肤感染，但提供了对致命性肺炎的保护。这些不同的结果与改变的免疫细胞募集无关，而是与毒素诱导的IL-1β产生缺陷相关。通过分析影响骨髓谱系和皮肤或肺上皮的ADAM 10双敲除小鼠来扩展这些研究，突出了毒素诱导的上皮损伤在控制感染结果中的突出性。总之，这些研究提供了成孔细胞毒素在调节宿主免疫力中作用的组织特异性的证据，并说明感染的结果是组织微环境中毒素所有作用的集体表现。
Immunomodulatory cytotoxins are prominent virulence factors produced by Staphylococcus aureus, a leading cause of bacterial sepsis, skin infection, and pneumonia. S. aureus α-toxin is a pore-forming toxin that utilizes a widely-expressed receptor, ADAM10, to injure the host epithelium, endothelium, and immune cells. As each host tissue is characterized by a unique composition of resident cells and recruited immune cells, the outcome of α-toxin-mediated injury may depend on the infected tissue environment. Utilizing myeloid lineage-specific Adam10 knockout mice, we show that α-toxin exerts tissue-specific effects on innate immunity to staphylococcal infection. Loss of ADAM10 expression exacerbates skin infection, yet affords protection against lethal pneumonia. These diverse outcomes are not related to altered immune cell recruitment, but rather correlate with a defect in toxin-induced IL-1β production. Extension of these studies through analysis of ADAM10 double knockout mice affecting both the myeloid lineage and either the skin or lung epithelium highlight the prominence of toxin-induced injury to the epithelium in governing the outcome of infection. Together, these studies provide evidence of tissue specificity of pore-forming cytotoxin action in modulation of host immunity, and illustrate that the outcome of infection is a collective manifestation of all effects of the toxin within the tissue microenvironment.
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影响因子：
3.1
作者：
BHAKDI, S;MUHLY, M;HUGO, F
通讯作者：
HUGO, F
DOI：
10.1073/pnas.0904958106
发表时间：
2009-08-04
影响因子：
11.1
作者：
Hruz, Petr;Zinkernagel, Annelies S.;Eckmann, Lars
通讯作者：
Eckmann, Lars
影响因子：
3
作者：
Clausen, BE;Burkhardt, C;Förster, I
通讯作者：
Förster, I
影响因子：
3.7
作者：
Brady, Rebecca A.;Mocca, Christopher P.;Burns, Drusilla L.
通讯作者：
Burns, Drusilla L.
影响因子：
6.4
作者：
Bartlett, Allison H.;Foster, Timothy J.;Park, Pyong Woo
通讯作者：
Park, Pyong Woo