Emerging Infectious Diseases

Biography

Biography: Tie Fu Liu

Abstract

Although the combined antiretroviral therapy signifi cantly improved the clinical outcomes of HIV/AIDS patients, the severe infl ammatory sepsis developed from the next infection became the leading cause of HIV/AIDS-related death. Th is is resulted from the infl ammatory priming of chronic HIV infection, which is characterized by the glucose transporter 1 (GLUT1) over-expression, hyperactivity of glycolysis in innate immune cells and constant pro-infl ammatory status. Th e underlying knowledge how the immunometabolic change during HIV infection primes severe infl ammatory sepsis is incomplete. We report here that the imbalance of pro- and anti-infl ammatory signaling is responsible for the priming of AIDS-related sepsis. Upon activation of TLR4 receptor by bacterial endotoxin, AIDS PBMCs highly expressed pro-infl ammatory cytokines comparing to the healthy PBMCs. Th is hyper pro-infl ammatory gene expression was contrary to the reduced expression of anti-infl ammatory SIRT1 and RelB, which constitutes the SIRT1- dependent antiinfl ammatory signaling. Stimulating SIRT1 activity by its activator resveratrol minimized expression of both TNF-☐ gene and cell surface GLUT1 of AIDS PBMCs in response to endotoxin stimulation. Mechanistically, resveratrol increased the nuclear abundance of anti-infl ammatory SIRT1 and RelB and reduced nuclear translocation of pro-infl ammatory NF☐B/ p65, thereby, preventing hyper pro-infl ammatory response upon subsequent endotoxin stimulation. Th us, restoring homeostasis of pro- and anti-infl ammatory signaling by activation of SIRT1-RelB immunometabolic axis promises prevention and eff ective therapy of AIDS-related sepsis. Th ese fi ndings should have translational impact on the severe infl ammatory priming in other chronic infl ammatory diseases.