» Articles » PMID: 37271505

Effects of Monophosphoryl Lipid A and Poly I:C Combination on Equine Cells

Overview
Journal J Vet Sci
Date 2023 Jun 4
PMID 37271505
Authors
Affiliations
Soon will be listed here.
Abstract

Background: Toll-like receptor (TLR) agonists have been used as adjuvants to modulate immune responses in both animals and humans.

Objectives: The objective of this study was to evaluate the combined effects of the TLR 4 agonist monophosphoryl lipid A (MPL) and the TLR 3 agonist polyinosinic:polycytidylic acid (Poly I:C) on equine peripheral blood mononuclear cells (PBMCs), monocyte-derived dendritic cells (MoDCs), and bone marrow-derived mesenchymal stromal cells (BM-MSCs).

Methods: The PBMCs, MoDCs, and BM-MSCs collected from three mixed breed horses were treated with MPL, Poly I:C, and their combination. The mRNA expression of interferon gamma (IFN-γ), interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-12p40, tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1) was determined using real-time polymerase chain reaction.

Results: The combination of MPL and Poly I:C significantly upregulated immunomodulatory responses in equine cells/ without cytotoxicity. The combination induced greater mRNA expression of pro-inflammatory cytokines IFN-γ and IL-6 than MPL or Poly I:C stimulation alone in PBMCs. In addition, the combination induced significantly higher mRNA expression of IL-1β, IL-6, and IL-12p40 in MoDCs, and IL-8, MCP-1, and VEGF in BM-MSCs compared to stimulation with a single TLR agonist.

Conclusions: The combination of MPL and Poly I:C can be used as a potential adjuvant candidate for vaccines to aid in preventing infectious diseases in horses.

References
1.
Whelan D, Caplice N, Clover A . Mesenchymal stromal cell derived CCL2 is required for accelerated wound healing. Sci Rep. 2020; 10(1):2642. PMC: 7021763. DOI: 10.1038/s41598-020-59174-1. View

2.
Thompson K, Strayer D, Salvato P, Thompson C, Klimas N, Molavi A . Results of a double-blind placebo-controlled study of the double-stranded RNA drug polyI:polyC12U in the treatment of HIV infection. Eur J Clin Microbiol Infect Dis. 1996; 15(7):580-7. DOI: 10.1007/BF01709367. View

3.
Seo J, Tsuzuki N, Haneda S, Yamada K, Furuoka H, Tabata Y . Osteoinductivity of gelatin/β-tricalcium phosphate sponges loaded with different concentrations of mesenchymal stem cells and bone morphogenetic protein-2 in an equine bone defect model. Vet Res Commun. 2014; 38(1):73-80. DOI: 10.1007/s11259-013-9587-5. View

4.
Figueiredo M, Vandenplas M, Hurley D, Moore J . Differential induction of MyD88- and TRIF-dependent pathways in equine monocytes by Toll-like receptor agonists. Vet Immunol Immunopathol. 2008; 127(1-2):125-34. DOI: 10.1016/j.vetimm.2008.09.028. View

5.
Hellman S, Hjertner B, Morein B, Fossum C . The adjuvant G3 promotes a Th1 polarizing innate immune response in equine PBMC. Vet Res. 2018; 49(1):108. PMC: 6389152. DOI: 10.1186/s13567-018-0602-2. View