The Interleukin-1β/CXCL1/2/Neutrophil Axis Mediates Host Protection against Group B Streptococcal Infection
The Interleukin-1β/CXCL1/2/Neutrophil Axis Mediates Host Protection against Group B Streptococcal Infection
复制标题
DOI：
10.1128/iai.02104-14
复制
发表时间：
2014-11-01
影响因子：
3.1
通讯作者：
Beninati, C.
中科院分区：
文献类型：
--
作者：
Biondo, C.;Mancuso, G.;Beninati, C.
先前的研究表明，B 族链球菌 (GBS) 是一种常见的人类病原体，可有效诱导白细胞介素 1 β (IL-1 β) 的释放，而白细胞介素 1 β 是炎症反应的重要介质。由于人们对这种细胞因子在 GBS 疾病中的作用知之甚少，我们分析了 IL-1 β 缺陷小鼠的感染结果。这些动物对 GBS 感染非常敏感，其中大多数在挑战条件下死亡，而野生型对照小鼠则没有死亡。致命性是由于 IL-1 β 缺陷小鼠无法控制局部 GBS 复制和传播到目标器官，如大脑和肾脏。此外，在腹膜内注射灭活的 GBS 诱导的炎症模型中，IL-1β 的缺乏与中性粒细胞趋化因子 CXCL1 和 CXCL2 的产生以及中性粒细胞向腹膜腔的募集的选择性损伤有关。在 IL-1 β 缺陷小鼠感染 GBS 期间，还观察到血液中性粒细胞计数减少，大脑和肾脏的中性粒细胞募集受损，同时 CXCL1 和 CXCL2 组织水平降低。值得注意的是，在免疫缺陷动物中观察到的对 GBS 感染的高度敏感性通过抗 Gr1 抗体消除中性粒细胞来重现。总的来说，我们的数据确定了一个细胞因子回路，该回路涉及 IL-1 β 诱导的 CXCL1 和 CXCL2 的产生，并导致中性粒细胞募集到 GBS 感染部位。此外，我们的数据表明这些细胞在控制 GBS 疾病的进展和结果中发挥着重要作用。
Previous studies have indicated that group B streptococcus (GBS), a frequent human pathogen, potently induces the release of interleukin-1 beta (IL-1 beta), an important mediator of inflammatory responses. Since little is known about the role of this cytokine in GBS disease, we analyzed the outcome of infection in IL-1 beta-deficient mice. These animals were markedly sensitive to GBS infection, with most of them dying under challenge conditions that caused no deaths in wild-type control mice. Lethality was due to the inability of the IL-1 beta-deficient mice to control local GBS replication and dissemination to target organs, such as the brain and the kidneys. Moreover, in a model of inflammation induced by the intraperitoneal injection of killed GBS, a lack of IL-1 beta was associated with selective impairment in the production of the neutrophil chemokines CXCL1 and CXCL2 and in neutrophil recruitment to the peritoneal cavity. Decreased blood neutrophil counts and impaired neutrophil recruitment to the brain and kidneys were also observed during GBS infection in IL-1 beta-deficient mice concomitantly with a reduction in CXCL1 and CXCL2 tissue levels. Notably, the hypersusceptibility to GBS infection observed in the immune-deficient animals was recapitulated by neutrophil depletion with anti-Gr1 antibodies. Collectively, our data identify a cytokine circuit that involves IL-1 beta-induced production of CXCL1 and CXCL2 and leads the recruitment of neutrophils to GBS infection sites. Moreover, our data point to an essential role of these cells in controlling the progression and outcome of GBS disease.