Inflammasome-mediated production of IL-1β is required for neutrophil recruitment against Staphylococcus aureus in vivo
Inflammasome-mediated production of IL-1β is required for neutrophil recruitment against Staphylococcus aureus in vivo
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DOI：
10.4049/jimmunol.179.10.6933
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发表时间：
2007-11-15
影响因子：
4.4
通讯作者：
Modlin, Robert L.
中科院分区：
文献类型：
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作者：
Miller, Lloyd S.;Pietras, Eric M.;Modlin, Robert L.
IL-1 R活化是在针对金黄色葡萄球菌感染的有效先天免疫应答中中性粒细胞募集所必需的。在本研究中，我们研究了IL-1 R在S.金黄色葡萄球菌感染。作为对S。金黄色葡萄球菌皮肤攻击后，与野生型小鼠相比，IL-1 β、IL-1 α/IL-1 β缺陷但IL-1 α不缺陷的小鼠出现更大的病变，细菌计数更高，中性粒细胞募集减少。神经元募集和细菌清除需要骨髓（BM）来源的细胞而不是非BM来源的驻留细胞表达IL-1 β。此外，缺乏炎性小体组分的小鼠在中性粒细胞募集和宿主防御方面具有与IL-1 β缺乏小鼠相同的缺陷，其中炎性小体组分包含半胱天冬酶募集结构域（ASC）的凋亡相关斑点样蛋白，这表明炎性小体在介导活性IL-1 β的产生以促进中性粒细胞募集宿主防御S.金黄色。重组活性IL-1，6在IL-1 β缺陷小鼠中控制感染和促进细菌清除的能力进一步支持了这一发现。这些研究定义了一个关键的宿主防御回路，其中由BM衍生的细胞产生的炎性小体介导的IL-1 β在非BM衍生的驻留细胞上发出IL-1 R信号，以激活针对S.金黄色葡萄球菌。
IL-1R activation is required for neutrophil recruitment in an effective innate immune response against Staphylococcus aureus infection. In this study, we investigated the mechanism of IL-1R activation in vivo in a model of S. aureus infection. In response to a S. aureus cutaneous challenge, mice deficient in IL-1 beta, IL-1 alpha/IL-1 beta, but not IL-1 alpha, developed larger lesions with higher bacterial counts and had decreased neutrophil recruitment compared with wild-type mice. Neutrophil recruitment and bacterial clearance required IL-1 beta expression by bone marrow (BM)-derived cells and not by non-BM-derived resident cells. In addition, mice deficient in the inflammasome component apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) had the same defects in neutrophil recruitment and host defense as IL-1 beta-deficient mice, demonstrating an essential role for the inflammasome in mediating the production of active IL-1 beta to promote neutrophil recruitment in host defense against S. aureus. This finding was further supported by the ability of recombinant active IL-1,6 to control the infection and promote bacterial clearance in IL-1 beta-deficient mice. These studies define a key host defense circuit where inflammasome-mediated IL-1 beta production by BM-derived cells signals IL-IR on non-BM-derived resident cells to activate neutrophil recruitment in the innate immune response against S. aureus in vivo.