Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, China.
Department of Laboratory Medicine, The Children's Hospital of Chongqing Medical University, Chongqing, China.
Front Immunol. 2020 Jan 21;10:3102. doi: 10.3389/fimmu.2019.03102. eCollection 2019.
Understanding of pathogenesis and protection mechanisms underlying influenza- pneumoniae co-infection may provide potential strategies for decreasing its high morbidity and mortality. Interleukin-6 (IL-6) is an important cytokine that acts to limit infection-related inflammation; however, its role in co-infected pneumonia remains unclear. Here we show that the clinically relevant co-infected mice displayed dramatically elevated IL-6 levels; which was also observed in patients with co-infected pneumonia. mice presented with increased bacterial burden, early dissemination of bacteria to extrapulmonary sites accompanied by aggravated pulmonary lesions and high mortality when co-infection. This protective function of IL-6 is associated with cellular death and macrophage function. Importantly, therapeutic administration of recombinant IL-6 protein reduced cells death in BALF, and enhanced macrophage phagocytosis through increased MARCO expression. This protective immune mechanism furthers our understanding of the potential impact of immune components during infection and provides potential therapeutic avenues for influenza- co-infected pneumonia.
了解流感-肺炎球菌合并感染的发病机制和保护机制可能为降低其高发病率和死亡率提供潜在策略。白细胞介素-6 (IL-6) 是一种重要的细胞因子，可限制感染相关炎症；然而，其在合并性肺炎中的作用尚不清楚。在这里，我们表明，临床上相关的合并感染小鼠表现出明显升高的 IL-6 水平；在合并性肺炎患者中也观察到了这种情况。当合并感染时， 小鼠表现出更高的细菌负荷，细菌早期向肺外部位扩散，同时伴有更严重的肺部病变和高死亡率。IL-6 的这种保护功能与细胞死亡和巨噬细胞功能有关。重要的是，重组 IL-6 蛋白的治疗性给药减少了 BALF 中的细胞死亡，并通过增加 MARCO 表达增强了巨噬细胞的吞噬作用。这种保护免疫机制进一步加深了我们对感染期间免疫成分潜在影响的理解，并为流感-合并感染性肺炎提供了潜在的治疗途径。
