Journal: Frontiers in Immunology
Article Title: Anti-PD-L1 therapy altered inflammation but not survival in a lethal murine hepatitis virus-1 pneumonia model
doi: 10.3389/fimmu.2023.1308358
Figure Lengend Snippet: Possible MHV-1 and PD-L1mAb molecular signals. Mouse hepatitis virus 1 (MHV-1) is a pneumotropic beta-coronavirus that produces severe acute respiratory syndrome (SARS)-like pathology in A/J mice. Intraperitoneal injected anti-PD-L1 antibodies (PD-L1mAb) or isotype antibodies (isomAb) were administered every third day, starting 12 days before and continuing until 3 days after intratracheal infection with saline vehicle control or 50 plaque-forming units (PFU)/mouse. The overall virus effect measured the MHV-1 effect in mice challenged with MHV-1 and treated with isomAb and PD-L1mAb. The overall treatment effect measured the effects of PD-L1mAb in MHV-1- and diluent (saline)-challenged mice. The challenge–treatment interaction measured the difference between the overall virus effect and the overall treatment effect. MHV-1 activates/phosphorylates AKT (pAKT). PD-L1mAb and/or MHV-1 induce the production of the S100A9 dimer, which also activates AKT. Downstream of AKT is hypoxia-inducible transcription factor (HIF)-1α, which induces the production of PD-L1, angiotensin-converting enzyme (ACE), and glucose transporter 1 (Glut1). Cellular uptake of glucose from the surrounding microenvironment is regulated by Glut1. Blood glucose levels are associated with ACE2 levels and both of these factors are down-regulated by PD-L1mAb and/or MHV-1. Increased ACE2 activity stabilizes FOXO1, whereas AKT phosphorylation of FOXO1 promotes FOXO1 degradation. FOXO1 is a PD-1 regulatory transcription factor.
Article Snippet: All animals prior to anesthesia for sample collection had anal temperatures (TCAT-2 temperature controller, Physitemp, Clifton, NJ, USA) and oxygen saturation (O 2 Sat), heart rate, and respiratory rate (MouseOx Plus Oximeter with pulse collar sensor, Starr Life Sciences, Oakmont, PA, USA) measured.
Techniques: Virus, Injection, Infection, Saline, Control, Activity Assay, Phospho-proteomics
