Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Research Centre of Infection and Immunology, The University of Hong Kong, Hong Kong, China.
J Infect Dis. 2019 Feb 15;219(5):795-807. doi: 10.1093/infdis/jiy527.
Obesity is associated with increased severity of influenza infection. However, the underlying mechanism is largely unknown.
We employed a mouse model with diet-induced obesity (DIO) to study the innate immune responses induced by influenza virus.
The lungs of DIO mice were heavily affected by obesity-associated chronic systemic inflammation with a significant increase in inflammatory cytokines/chemokines. Concurrently, lipid immune mediator prostaglandin E2 (PGE2) was also significantly elevated in DIO mice. However, the DIO mice mounted a blunted and delayed upregulation of mRNA and protein concentrations of interferon-β and inflammatory cytokines/chemokines upon A(H1N1)pdm09 virus (H1N1/415742Md) challenge compared with those of lean mice. PGE2 concentrations were significantly higher in the lungs of DIO mice compared to that of lean mice postchallenge. Treatment with paracetamol in challenged DIO mice significantly enhanced the expression of interferon-α/β and cytokine genes at days 1 and 3 postinfection compared with that of untreated DIO mice. Furthermore, paracetamol treatment alone started 3 days before virus challenge and continued until 6 days postchallenge ameliorated the severity of a lethal H1N1/415742Md infection in DIO mice with improved survival.
Impaired innate response to influenza in DIO mice is associated with elevated PGE2, which could be restored to some degree by paracetamol treatment.
肥胖与流感感染的严重程度增加有关。然而，其潜在机制在很大程度上尚不清楚。
我们采用饮食诱导肥胖（DIO）的小鼠模型来研究流感病毒诱导的固有免疫反应。
肥胖相关的慢性全身性炎症使 DIO 小鼠的肺部受到严重影响，炎症细胞因子/趋化因子显著增加。同时，脂质免疫介质前列腺素 E2（PGE2）在 DIO 小鼠中也显著升高。然而，与瘦小鼠相比，DIO 小鼠在 A（H1N1）pdm09 病毒（H1N1/415742Md）挑战后干扰素-β和炎症细胞因子/趋化因子的 mRNA 和蛋白浓度的上调明显减弱和延迟。与瘦小鼠相比，DIO 小鼠感染后肺部的 PGE2 浓度明显更高。与未治疗的 DIO 小鼠相比，用扑热息痛治疗感染的 DIO 小鼠可显著增强感染后第 1 天和第 3 天干扰素-α/β和细胞因子基因的表达。此外，在病毒攻击前 3 天开始单独用扑热息痛治疗并持续至感染后 6 天，可改善 DIO 小鼠致命性 H1N1/415742Md 感染的严重程度，提高存活率。
DIO 小鼠对流感的固有反应受损与 PGE2 升高有关，扑热息痛治疗可在一定程度上恢复。
