Inhibition of cGAS aggravated the host inflammatory response to Aspergillus fumigatus

作者全名："Peng, Mei; Li, Xiujun; Zhang, Xiaobing; Peng, Li"

作者地址："[Peng, Mei; Peng, Li] Chongqing Med Univ, Dept Resp & Crit Care Med, Affiliated Hosp 1, Chongqing, Peoples R China; [Li, Xiujun] Chongqing Med Univ, Coll Basic Med, Dept Pathol, Chongqing, Peoples R China; [Zhang, Xiaobing] Chongqing Med Univ, Dept Lab Med, Affiliated Hosp 1, Chongqing, Peoples R China; [Peng, Li] Chongqing Med Univ, Dept Resp & Crit Care Med, Affiliated Hosp 1, 1 Youyi Rd, Chongqing, Peoples R China"

通信作者："Peng, L (通讯作者)，Chongqing Med Univ, Dept Resp & Crit Care Med, Affiliated Hosp 1, 1 Youyi Rd, Chongqing, Peoples R China."

来源：EXPERIMENTAL LUNG RESEARCH

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000987546800001

JCR分区：Q3

影响因子：1.5

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Aspergillus fumigatus (A; fumigatus); cGAS; cGAS-STING signaling pathway; Fungal; Invasive pulmonary aspergillosis (IPA)

摘要："Backgroud: Aspergillus fumigatus (A. fumigatus) is a clinically important fungal pathogen. Invasive pulmonary aspergillosis (IPA) is the main fungal infection with increased morbidity and mortality in immunocompromised populations, although treatments are available. An innate DNA sensor known as cyclic GMP-AMP Synthase (cGAS) has recently been discovered that senses invading pathogens and has a significant impact on innate immunity. It can activate the cGAS-STING signaling pathway to stimulate downstream signals. But it is still unclear what role it plays in IPA's pathogenesis.Methods: An investigation into the infection of A. fumigatus was conducted by inhibiting cGAS activity in vivo and in vitro using siRNA and RU.521(an inhibitor of cGAS).Results: We discovered that suppressing cGAS increased the host's susceptibility to A. fumigatus and harmed those with infections by enhancing pulmonary tissue damage and edema, as well as decreasing fungal clearance. Furthermore, our findings show that inhibiting or silencing cGAS can exacerbate the inflammatory response in IPA mouse models and human bronchi epithelial cells (HBECs) treated with A. fumigatus by upregulating the production of inflammatory genes with non-type 1 interferon.Conclusion: Based on our analysis, we conclude that activating cGAS might increase host resistance to A. fumigatus, protect against pulmonary illnesses brought on by A. fumigatus and that exploring the cGAS-STING signaling pathway is beneficial not only for the immunological investigation of IPA but also may be a potential therapeutic objective."

基金机构：Chongqing Health and Family Planning Committee [2017ZDXM004]

基金资助正文：This research received financial support from the Chongqing Health and Family Planning Committee (2017ZDXM004).