Interleukin-1β Regulates CXCL8 Release and Influences Disease Outcome in Response to Streptococcus pneumoniae, Defining Intercellular Cooperation between Pulmonary Epithelial Cells and Macrophages
Interleukin-1β Regulates CXCL8 Release and Influences Disease Outcome in Response to Streptococcus pneumoniae, Defining Intercellular Cooperation between Pulmonary Epithelial Cells and Macrophages
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DOI：
10.1128/iai.05697-11
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发表时间：
2012-03-01
影响因子：
3.1
通讯作者：
Dockrell, David H.
中科院分区：
文献类型：
--
作者：
Marriott, Helen M.;Gascoyne, Kate A.;Dockrell, David H.
肺炎链球菌（肺炎球菌）作为肺部病原体的成功与其限制呼吸道上皮细胞的先天免疫反应有关。用于克服这种限制的机制是不完全阐明。肺趋化因子的表达涉及复杂的细胞和分子网络，涉及肺上皮，但具体的细胞相互作用和控制它们的细胞因子是不完全确定的。我们发现，即使在没有多糖荚膜的情况下，血清2型或4型肺炎球菌也仅诱导上皮细胞系中CXCL 8的适度表达。相反，A549细胞与巨噬细胞样THP-1细胞系，维生素D分化，或单核细胞衍生的巨噬细胞共培养增强CXCL 8的释放。来自THP-1细胞系的上清液引发A549细胞以类似于共培养物的水平释放CXCL 8。白细胞介素-1 Ra（IL-1 Ra）抑制共培养物中CXCL 8的释放并降低巨噬细胞条件培养基的活性，但肿瘤坏死因子α（TNF-alpha）的抑制对CXCL 8的释放影响很小。在共培养物中，IL-1 β而非TNF-α的释放上调。IL-1 1型受体敲除C57 BL/6和BALB/c小鼠证实了IL-1信号传导在体内CXC趋化因子表达和中性粒细胞募集中的重要性。在暴发性疾病中，IL-1信号的增加导致气道中中性粒细胞的增加和更具侵袭性的疾病。这些结果表明，IL-1是涉及巨噬细胞和上皮细胞的细胞网络的重要组成部分，其促进CXC趋化因子表达并在肺炎球菌肺炎期间辅助中性粒细胞募集。他们还强调了抗IL-1治疗在限制肺部过度嗜酸性炎症方面的潜在临床作用。
The success of Streptococcus pneumoniae (the pneumococcus) as a pulmonary pathogen is related to its restriction of innate immune responses by respiratory epithelial cells. The mechanisms used to overcome this restriction are incompletely elucidated. Pulmonary chemokine expression involves complex cellular and molecular networks, involving the pulmonary epithelium, but the specific cellular interactions and the cytokines that control them are incompletely defined. We show that serotype 2 or 4 pneumococci induce only modest levels of CXCL8 expression from epithelial cell lines, even in the absence of a polysaccharide capsule. In contrast, coculture of A549 cells with the macrophage-like THP-1 cell line, differentiated with vitamin D, or monocyte-derived macrophages enhanced CXCL8 release. Supernatants from the THP-1 cell line prime A549 cells to release CXCL8 at levels similar to cocultures. Interleukin-1Ra (IL-1Ra) inhibits CXCL8 release from cocultures and reduces the activity of macrophage-conditioned media, but inhibition of tumor necrosis factor alpha (TNF-alpha) had only a minimal effect on CXCL8 release. Release of IL-1 beta but not TNF-alpha was upregulated in cocultures. IL-1 type 1 receptor knockout C57BL/6 and BALB/c mice confirmed the importance of IL-1 signaling in CXC chemokine expression and neutrophil recruitment in vivo. In fulminant disease, increased IL-1 signaling resulted in increased neutrophils in the airway and more invasive disease. These results demonstrate that IL-1 is an important component of the cellular network involving macrophages and epithelial cells, which facilitates CXC chemokine expression and aids neutrophil recruitment during pneumococcal pneumonia. They also highlight a potential clinical role for anti-IL-1 treatment to limit excessive neutrophilic inflammation in the lung.