Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USA.
Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA.
Nat Immunol. 2019 Feb;20(2):129-140. doi: 10.1038/s41590-018-0288-7. Epub 2019 Jan 21.
Basophils are evolutionarily conserved in vertebrates, despite their small numbers and short life span, suggesting that they have beneficial roles in maintaining health. However, these roles are not fully defined. Here we demonstrate that basophil-deficient mice exhibit reduced bacterial clearance and increased morbidity and mortality in the cecal ligation and puncture (CLP) model of sepsis. Among the several proinflammatory mediators that we measured, tumor necrosis factor (TNF) was the only cytokine that was significantly reduced in basophil-deficient mice after CLP. In accordance with that observation, we found that mice with genetic ablation of Tnf in basophils exhibited reduced systemic concentrations of TNF during endotoxemia. Moreover, after CLP, mice whose basophils could not produce TNF, exhibited reduced neutrophil and macrophage TNF production and effector functions, reduced bacterial clearance, and increased mortality. Taken together, our results show that basophils can enhance the innate immune response to bacterial infection and help prevent sepsis.
嗜碱性粒细胞在脊椎动物中是进化保守的，尽管它们数量少，寿命短，但这表明它们在维持健康方面具有有益的作用。然而，这些作用尚未完全确定。在这里，我们证明了嗜碱性粒细胞缺陷小鼠在盲肠结扎和穿孔 (CLP) 败血症模型中表现出细菌清除减少和发病率和死亡率增加。在我们测量的几种促炎介质中，肿瘤坏死因子 (TNF) 是 CLP 后嗜碱性粒细胞缺陷小鼠中唯一显著减少的细胞因子。与该观察结果一致，我们发现嗜碱性粒细胞中 Tnf 基因缺失的小鼠在内毒素血症期间表现出 TNF 的全身浓度降低。此外，在 CLP 后，无法产生 TNF 的嗜碱性粒细胞的小鼠表现出中性粒细胞和巨噬细胞 TNF 产生和效应功能降低、细菌清除减少和死亡率增加。综上所述，我们的结果表明嗜碱性粒细胞可以增强对细菌感染的固有免疫反应，并有助于预防败血症。
