Histone acetylation regulates BMMCs recognition of foot-and-mouth disease virus-like particles

Abstract

Foot-and-mouth disease (FMD) is one of the most economically and socially devastating diseases affecting animal agriculture worldwide. Foot-and-mouth disease virus (FMDV) virus-like particles (VLPs) have been widely studied as a candidate vaccine. Mast cells (MCs) are highly versatile innate immunity cells that perform various functions in regulating innate and adaptive immune responses. Recently, we found that MCs can recognize recombinant FMDV VP1-VP4 protein to produce various cytokines with differential expression, suggesting that this may be epigenetically regulated. In this study, we evaluated the effect of trichostatin A (TSA), a histone deacetylase inhibitor, on bone marrow-derived mast cells (BMMCs) recognition of FMDV-VLPs in vitro. BMMCs can recognize FMDV-VLPs via mannose receptors (MRs) and resulted in enhanced expression and secretion of tumour necrosis factor α (TNF-α) and interleukin (IL)-13. Nevertheless, BMMCs recognition of FMDV-VLPs to secrete IL-6 was irrelevant to MRs, and MRs may play a negative regulation for IL-10 secretion. Pre-treatment with TSA caused decreased expression of IL-6, TNF-α and IL-13, and increased expression of IL-10. Furthermore, the expression of nuclear factor-kappa B (NF-κB) was supressed in TSA treated BMMCs, suggesting histone acetylation may alter NF-κB expression to influence the TNF-α and IL-13 secretion. Pre-treatment with TSA had no influence on the expression of microphthalmia-associated transcription factor (MITF) and GATA-2. These data therefore suggest that altered histone acetylation regulates the immune responses induced by BMMCs recognition of FMDV-VLPs, providing an understanding and theory basis for the prevention and control of FMD based MCs.

Keywords: Cytokines; Foot-and-mouth disease virus-like particles; Histone acetylation; Mannose receptors; Mast cells.