Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, China; School of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, China; School of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
Int Immunopharmacol. 2019 Sep;74:105710. doi: 10.1016/j.intimp.2019.105710. Epub 2019 Jun 27.
Type I interferon (IFN) is indispensable for antiviral immunity, but its role in bacterial infections is controversial and not fully described. Nontypeable Haemophilus influenzae (NTHi) is one of the most common bacterial pathogens in patients with chronic obstructive pulmonary disease (COPD). NTHi-DNA activates type I IFN production in macrophages, but the function of type I IFN in host-pathogen interactions, in the context of NTHi infection, is still unclear. Here, we showed that type I IFN, induced by NTHi-DNA, restrained bacterial killing in vitro and promoted COPD development in vivo in response to NTHi. Mice deficient for type I IFN receptor (IFNAR) exhibited improved resistance to NTHi infection. Moreover, similar to exogenous IFN-β, NTHi-DNA-induced type I IFN increased the production of IL-6, IL-1β, IL-12 and CXCL10 via p38 MAPK activation. Our findings demonstrated that NTHi-DNA-induced type I IFN signaling played a negative role in host defense against NTHi infection and identified potential targets for future therapeutic management of COPD.
I 型干扰素（IFN）对于抗病毒免疫是必不可少的，但它在细菌感染中的作用存在争议，尚未得到充分描述。无荚膜流感嗜血杆菌（NTHi）是慢性阻塞性肺疾病（COPD）患者中最常见的细菌病原体之一。NTHi-DNA 可激活巨噬细胞中 I 型 IFN 的产生，但在 NTHi 感染的情况下，I 型 IFN 在宿主-病原体相互作用中的功能仍不清楚。在这里，我们表明，NTHi-DNA 诱导的 I 型 IFN 抑制了体外细菌杀伤，并促进了体内对 NTHi 的 COPD 发展。缺乏 I 型 IFN 受体（IFNAR）的小鼠对 NTHi 感染的抵抗力增强。此外，与外源性 IFN-β 类似，NTHi-DNA 诱导的 I 型 IFN 通过 p38 MAPK 激活增加了 IL-6、IL-1β、IL-12 和 CXCL10 的产生。我们的研究结果表明，NTHi-DNA 诱导的 I 型 IFN 信号在宿主防御 NTHi 感染方面发挥了负面作用，并确定了 COPD 未来治疗管理的潜在靶点。
