Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing, China.
Department of Laboratory Medicine, Guiyang Maternity & Child Health Hospital, Guiyang, China.
Front Immunol. 2021 Apr 19;12:624775. doi: 10.3389/fimmu.2021.624775. eCollection 2021.
() is a common respiratory pathogen and a frequent cause of acute otitis media (AOM) in children. However, little is known about the immunometabolism during AOM. This study was to assess the presence of glucose metabolic reprogramming during AOM and its underlying mechanism affecting inflammatory response and middle ear injury.
The levels of glycolytic metabolism were evaluated by measuring the expression of glycolysis-related genes and the production of metabolites. HE stain, immunofluorescence, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and Western blot were performed to measure the effect of glucose metabolic reprogramming on inflammatory response, pneumococcal clearance, hypoxia-inducible factor 1 alpha (HIF-1α) expression and cytokine secretion during AOM, respectively.
The analysis of microarray revealed an increase of the expression of glycolysis-related genes during -induced AOM, which was verified by real-time PCR. Increased glycolysis promoted the production of IL-1β and TNF-α and facilitated the clearance of by enhancing phagocytosis and killing capability of neutrophils, but also aggravated the middle ear injury. Furthermore, these pathogenic effects could be reversed after glycolytic inhibitor 2DG treatment. Additionally, HIF-1α was observed to involve in glycolytic metabolism during AOM.
infection induced increased glycolysis conversion during AOM, which promoted inflammatory responses and bacterial clearance, but also aggravated tissue damage.
肺炎链球菌（）是一种常见的呼吸道病原体，也是儿童急性中耳炎（AOM）的常见病因。然而，关于 AOM 期间的免疫代谢情况知之甚少。本研究旨在评估 AOM 期间是否存在葡萄糖代谢重编程及其影响炎症反应和中耳损伤的潜在机制。
通过测量糖酵解相关基因的表达和代谢物的产生来评估糖酵解代谢水平。进行 HE 染色、免疫荧光、免疫组织化学、酶联免疫吸附测定（ELISA）和 Western blot，分别测量葡萄糖代谢重编程对 AOM 期间炎症反应、肺炎链球菌清除、缺氧诱导因子 1 ɑ（HIF-1ɑ）表达和细胞因子分泌的影响。
微阵列分析显示，在 -诱导的 AOM 期间，糖酵解相关基因的表达增加，实时 PCR 验证了这一点。增加的糖酵解促进了白细胞介素 1β（IL-1β）和肿瘤坏死因子-α（TNF-α）的产生，并通过增强中性粒细胞的吞噬和杀伤能力促进了 的清除，但也加重了中耳损伤。此外，在使用糖酵解抑制剂 2DG 治疗后，这些致病作用可以逆转。此外，还观察到在 AOM 期间 HIF-1ɑ参与糖酵解代谢。
感染诱导 AOM 期间增加的糖酵解转化，促进了炎症反应和细菌清除，但也加重了组织损伤。
