Millennium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Servicio de Anatomía Patológica, Hospital Barros Luco Trudeau, Santiago, Chile.
Front Immunol. 2021 Apr 28;12:638917. doi: 10.3389/fimmu.2021.638917. eCollection 2021.
Neutrophils are immune cells classically defined as pro-inflammatory effector cells. However, current accumulated evidence indicates that neutrophils have more versatile immune-modulating properties. During acute lung infection with in mice, interleukin-10 (IL-10) production is required to temper an excessive lung injury and to improve survival, yet the cellular source of IL-10 and the immunomodulatory role of neutrophils during infection remain unknown. Here we show that neutrophils are the main myeloid cells that produce IL-10 in the lungs during the first 48 h of infection. Importantly, assays with bone-marrow derived neutrophils confirmed that IL-10 can be induced by these cells by the direct recognition of pneumococcal antigens. , we identified the recruitment of two neutrophil subpopulations in the lungs following infection, which exhibited clear morphological differences and a distinctive profile of IL-10 production at 48 h post-infection. Furthermore, adoptive transfer of neutrophils from WT mice into IL-10 knockout mice ( ) fully restored IL-10 production in the lungs and reduced lung histopathology. These results suggest that IL-10 production by neutrophils induced by limits lung injury and is important to mediate an effective immune response required for host survival.
中性粒细胞是经典定义的免疫细胞,作为促炎效应细胞。然而,目前积累的证据表明,中性粒细胞具有更通用的免疫调节特性。在小鼠的急性肺部感染中,白细胞介素-10(IL-10)的产生需要缓和过度的肺部损伤并提高存活率,但 IL-10 的细胞来源以及中性粒细胞在感染中的免疫调节作用仍不清楚。在这里,我们表明中性粒细胞是在感染后前 48 小时肺部产生 IL-10 的主要髓样细胞。重要的是,用骨髓衍生的中性粒细胞进行的实验证实,这些细胞可以通过对肺炎球菌抗原的直接识别来诱导产生 IL-10。此外,我们发现感染后肺部有两种中性粒细胞亚群的募集,它们在 48 小时时表现出明显的形态差异和独特的 IL-10 产生特征。此外,将来自 WT 小鼠的中性粒细胞过继转移到 IL-10 敲除小鼠()中,可完全恢复肺部的 IL-10 产生并减轻肺部组织病理学变化。这些结果表明,肺炎球菌诱导的中性粒细胞产生的 IL-10 可限制肺部损伤,对于介导宿主存活所需的有效免疫反应很重要。