Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, K7L 3N6, Canada.
Sci Rep. 2018 Sep 12;8(1):13704. doi: 10.1038/s41598-018-32007-y.
Cytokine responses from monocytes and macrophages exposed to bacteria are of particular importance in innate immunity. Focusing on the impact of the immunoregulatory cytokine interleukin (IL)-27 on control of innate immune system responses, we examined human immune responses to bacterial products and bacterial infection by E. coli and S. typhimurium. Since the effect of IL-27 treatment in human myeloid cells infected with bacteria is understudied, we treated human monocytes and macrophages with IL-27 and either LPS, flagellin, or bacteria, to investigate the effect on inflammatory signaling and cytokine responses. We determined that simultaneous stimulation with IL-27 and LPS derived from E. coli or S. typhimurium resulted in enhanced IL-12p40, TNF-α, and IL-6 expression compared to that by LPS alone. To elucidate if IL-27 manipulated the cellular response to infection with bacteria, we infected IL-27 treated human macrophages with S. typhimurium. While IL-27 did not affect susceptibility to S. typhimurium infection or S. typhimurium-induced cell death, IL-27 significantly enhanced proinflammatory cytokine production in infected cells. Taken together, we highlight a role for IL-27 in modulating innate immune responses to bacterial infection.
细胞因子反应来自于暴露于细菌的单核细胞和巨噬细胞，在先天免疫中尤为重要。我们专注于免疫调节细胞因子白细胞介素（IL）-27对先天免疫系统反应的控制作用，研究了人类对细菌产物和大肠杆菌及鼠伤寒沙门氏菌感染的免疫反应。由于 IL-27 对细菌感染的人类髓样细胞的作用研究不足，我们用 IL-27 处理人单核细胞和巨噬细胞，并用 LPS、鞭毛蛋白或细菌进行处理，以研究其对炎症信号和细胞因子反应的影响。我们发现，与单独用 LPS 刺激相比，同时用来自大肠杆菌或鼠伤寒沙门氏菌的 IL-27 和 LPS 刺激导致 IL-12p40、TNF-α 和 IL-6 的表达增强。为了阐明 IL-27 是否操纵了对细菌感染的细胞反应，我们用鼠伤寒沙门氏菌感染经 IL-27 处理的人巨噬细胞。虽然 IL-27 不影响对鼠伤寒沙门氏菌感染的易感性或鼠伤寒沙门氏菌诱导的细胞死亡，但 IL-27 显著增强了感染细胞中促炎细胞因子的产生。总之，我们强调了 IL-27 在调节对细菌感染的先天免疫反应中的作用。
