Effect of Cytomegalovirus Recombinant Phosphoprotein 150 (pp150) on Maturation and Function of Murine Dendritic Cells: an In-Vitro Study

Iran J Immunol. 2020 Mar;17(1):26-40. doi: 10.22034/iji.2020.80292.

Abstract

Background: Tegument protein pp150 of cytomegaloviruses (CMVs) plays a vital role in all stages of viral life cycle, representing the most important tegument protein candidate for HCMV treatment. However, the exact role of pp150 in immune regulation is yet to be elucidated.

Objective: To examine the effects of pp150 on the maturity and function of murine dendritic cells (DCs).

Methods: Maturity status (CD40, CD86, and MHC-II expression) and phagocytic capacity of DCs (dextran uptake assay) were characterized. Gene expression profiles of ROR-γ, GATA-3, T-bet, and FOXP-3 as well as the protein expression of INF-γ (Th1), IL-4 (Th2), IL-35 (Treg), IL-17A (Th17), IL-22, TNF-α, IL-6, and IL-2 were evaluated in T cells co-cultured with DCs.

Results: A significant increase in CD40, CD86, and CCR7 expression and a reduction in the phagocytosis rate were observed in pp150-stimulated DCs compared with unstimulated DCs. T cells co-cultured with stimulated DCs showed higher expressions of ROR-γ, IL-6, IL-2, IL-17A, IL-22, and TNF-α.

Conclusion: Despite improvements in maturity status, pp150-stimulated DCs did not seem to be able to induce Th1 or Th2 immunity. In fact, Th17 and its mediators, IL-17A and IL-22, might be the main inflammatory factors involved in pp150-stimulated DC's mechanism of action. However, it is necessary to conduct further investigations to corroborate these observations.

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Female
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Phosphoproteins / immunology*
  • Phosphoproteins / pharmacology
  • Recombinant Proteins / immunology
  • Recombinant Proteins / pharmacology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Viral Matrix Proteins / immunology*
  • Viral Matrix Proteins / pharmacology

Substances

  • Phosphoproteins
  • Recombinant Proteins
  • Viral Matrix Proteins
  • pp150 protein, Cytomegalovirus