Inhibition of cGAS aggravated the host inflammatory response to .

() 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. An investigation into the infection of was conducted by inhibiting cGAS activity and using siRNA and RU.521(an inhibitor of cGAS). We discovered that suppressing cGAS increased the host's susceptibility to 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 by upregulating the production of inflammatory genes with non-type 1 interferon. Based on our analysis, we conclude that activating cGAS might increase host resistance to , protect against pulmonary illnesses brought on by 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.