SiOprompts host defense against Acinetobacter baumannii infection by mTORC1 activation.

Abstract

Host-pathogen interactions in the setting of chronic pulmonary inflammation remain unclear, and the occurrence of pneumonia is increased in patients with chronic obstructive pulmonary disease who use immunosuppressive drugs. We performed Acinetobacter baumannii infection in mice with chronic pulmonary inflammation after intranasal administration of SiOand found SiOtreatment increased host defense against A. baumannii infection. Innate immune responses initiated by NF-κB, type 1 interferon, NLRP3 and AIM2 inflammasomes were dispensable for SiO-mediated host defense. SiOtreatment activated the mTORC1 signaling, and mTORC1 was crucial for host defense against A. baumannii infection. Our study highlights the protective role of mTORC1 signaling in host defense against bacterial infection, offers novel insights into understanding the mechanisms of immunosuppressive drug-related pneumonia, and provides potential host-directed therapeutics to treat bacterial infections.