Allium sativum‐derived allitridin inhibits treg amplification in cytomegalovirus infection

This study investigated the effects of allitridin compound on murine cytomegalovirus (MCMV)‐induced regulatory T cell (Treg; CD4⁺CD25⁺Foxp3⁺) amplification in vivo and in vitro. One hundred twenty MCMV‐infected mice were allocated at random into two groups for treatment with allitridin or placebo. Another 120 mock‐infected mice were randomly allocated as controls for the allitridin treatment and placebo treatment groups. The mice were euthanized at various time points after infection (out to 120 days) to evaluate the effects of treatment on Treg presence and function, as well as MCMV infective load. Co‐culture with mouse embryo fibroblasts (MEF) and MCMV was performed to evaluate allitridin‐mediated Treg and anti‐CMV effects. The maximum tolerance concentration (MTC) of allitridin was used to treat cells for 3 days. Changes in Foxp3 mRNA and protein levels, percentages of T cell subsets, and Treg‐related cytokines (IL‐10 and TGF‐β) were measured. Allitridin treatment did not influence Foxp3 expression and Treg proportion in uninfected mice, but did down‐regulate each in infected mice during the chronic infection period. Additionally, allitridin treatment reduced the MCMV load in salivary glands. MTC allitridin treatment of co‐cultures partially blocked MCMV induction of Foxp3 mRNA and protein expression. In vitro treatment with allitridin also increased significantly the percentages of Tc1, Tc2, and Th1, reduced the secreted levels of IL‐10 and TGF‐β1, and significantly suppressed viral loads. In conclusion, allitridin can promote MCMV‐induced Treg expansion and Treg‐mediated anti‐MCMV immunosuppression. Therefore, allitridin may be useful as a therapeutic agent to enhance the specific cellular immune responses against CMV. J. Med. Virol. 85:493–500, 2013. © 2013 Wiley Periodicals, Inc.