Artesunate interacts with Vitamin D receptor to reverse mouse model of sepsis-induced immunosuppression via enhancing autophagy

Shenglan Shang; Jiaqi Wu; Xiaoli Li; Xin Liu; Pan Li; Chunli Zheng; Yonghua Wang; Songqing Liu; Jiang Zheng; Hong Zhou

In the course of sepsis, both innate and acquired immune systems are involved in its development, in which the mononuclear phagocyte system plays a crucial role. Although the timeline of immunological alterations in sepsis is not well understood, the suggestive evidence demonstrated that the development of sepsis involves two distinct stages, an initial cytokine storm (hyper-inflammation) and subsequent immunosuppression (hypo-inflammation), which exist concomitantly and dominate in different stage (Hotchkiss, Monneret & Payen, 2013a; Hutchins, Unsinger, Hotchkiss & Ayala, 2014) . The uncontrolled cytokine storm is responsible for deaths occurring within the first few days, whereas immunosuppression predominantly causes mortality during the later stage of sepsis. In fact, more than 70% of patients die after the first three days of sepsis, which might due to the increased susceptibility to weakly virulent pathogens or opportunistic bacteria (e.g., Pseudomonas aeruginosa), indicating a failure of the host to eradicate invading pathogens (Hotchkiss, Monneret & Payen, 2013a; Skrupky, Kerby & Hotchkiss, 2011) . For patients in immunosuppression stage, only less than 5% of monocytes/macrophages produce cytokines, . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi. org/10.1101 org/10. /2020 which might be related to the disordered immune response in sepsis (Hotchkiss, Monneret & Payen, 2013a; Hutchins, Unsinger, Hotchkiss & Ayala, 2014) , demonstrating the impaired function of monocytes/macrophages is tightly related to the decrease of removing bacteria.