Prostaglandin E2 -Induced Immune Exhaustion and Enhancement of Antiviral Effects by Anti-PD-L1 Antibody Combined with COX-2 Inhibitor in Bovine Leukemia Virus Infection

The Journal of Immunology : Official Journal of the American Association of Immunologists
Yamato SajikiKazuhiko Ohashi

Abstract

Bovine leukemia virus (BLV) infection is a chronic viral infection of cattle and endemic in many countries, including Japan. Our previous study demonstrated that PGE2, a product of cyclooxygenase (COX) 2, suppresses Th1 responses in cattle and contributes to the progression of Johne disease, a chronic bacterial infection in cattle. However, little information is available on the association of PGE2 with chronic viral infection. Thus, we analyzed the changes in plasma PGE2 concentration during BLV infection and its effects on proviral load, viral gene transcription, Th1 responses, and disease progression. Both COX2 expression by PBMCs and plasma PGE2 concentration were higher in the infected cattle compared with uninfected cattle, and plasma PGE2 concentration was positively correlated with the proviral load. BLV Ag exposure also directly enhanced PGE2 production by PBMCs. Transcription of BLV genes was activated via PGE2 receptors EP2 and EP4, further suggesting that PGE2 contributes to disease progression. In contrast, inhibition of PGE2 production using a COX-2 inhibitor activated BLV-specific Th1 responses in vitro, as evidenced by enhanced T cell proliferation and Th1 cytokine production, and reduced BLV proviral load in vi...Continue Reading

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Citations

Jul 24, 2020·British Journal of Pharmacology·Calum T RobbChengcan Yao
Nov 21, 2020·PloS One·Otgontuya GanbaatarKazuhiko Ohashi
Jan 29, 2021·Mediators of Inflammation·Feiyang CaiGuangjie Chen
Feb 9, 2021·Advanced Science·Xiangyu DengYanli Zhao
Dec 22, 2020·Frontiers in Veterinary Science·Yamato SajikiKazuhiko Ohashi
Dec 10, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Tina BormannUlrich A Maus
Mar 26, 2021·International Immunopharmacology·Xiaoxu Li, Wenling Zhang
Apr 16, 2021·Veterinary Immunology and Immunopathology·Y SajikiK Ohashi
Aug 5, 2021·PloS One·Melanie Ricke-HochDenise Hilfiker-Kleiner
Sep 6, 2020·Developmental and Comparative Immunology·Yamato SajikiKazuhiko Ohashi
Sep 28, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Milad AshrafizadehRajender S Varma

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