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 ...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 SiO_(2) and found SiO_(2) treatment 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_(2)-mediated host defense.SiO_(2)treatment 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.展开更多
基金supported by the National Key Research and Development Program of China(2017YFD0500300)the National Natural Science Foundation of China(31970896,31701134 and 81701578)Yunnan Province(2019FJ008,2018FA038,2018FB127,2018FB131,HXDTZX-2019-1,HXDT-2019-2,and AMHD-2018-2)。
文摘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 SiO_(2) and found SiO_(2) treatment 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_(2)-mediated host defense.SiO_(2)treatment 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.
