Deoxynivalenol Affects Proliferation and Expression of Activation-Related Molecules in Major Porcine T-Cell Subsets.

Vatzia Vatzia,Pierron Pierron,Gerner Gerner,Saalmüller Saalmüller,Mayer Mayer

doi:10.3390/toxins11110644

Vatzia Vatzia, Pierron Pierron + Show 3 more

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https://doi.org/10.3390/toxins11110644

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Journal: Toxins	Publication Date: Nov 5, 2019
Citations: 15	License type: CC BY 4.0

Affiliation: University of Veterinary Medicine Vienna

Abstract

The Fusarium mycotoxin deoxynivalenol (DON) contaminates animal feed worldwide. In vivo, DON modifies the cellular protein synthesis, thereby also affecting the immune system. However, the functional consequences of this are still ill-defined. In this study, peripheral blood mononuclear cells from healthy pigs were incubated with different DON concentrations in the presence of Concanavalin A (ConA), a plant-derived polyclonal T-cell stimulant. T-cell subsets were investigated for proliferation and expression of CD8α, CD27, and CD28, which are involved in activation and costimulation of porcine T cells. A clear decrease in proliferation of all ConA-stimulated major T-cell subsets (CD4+, CD8+, and γδ T cells) was observed in DON concentrations higher than 0.4 µM. This applied in particular to naïve CD4+ and CD8+ T cells. From 0.8 μM onwards, DON induced a reduction of CD8α (CD4+) and CD27 expression (CD4+ and CD8+ T cells). CD28 expression was diminished in CD4+ and CD8+ T cells at a concentration of 1.6 µM DON. None of these effects were observed with the DON-derivative deepoxy-deoxynivalenol (DOM-1) at 16 µM. These results indicate that DON reduces T-cell proliferation and the expression of molecules involved in T-cell activation, providing a molecular basis for some of the described immunosuppressive effects of DON.

Highlights

The Fusarium mycotoxin deoxynivalenol (DON) is a secondary fungal metabolite, which contaminates cereal-based foods worldwide and, is considered as a threat for public health and for the nutrition of farm animals [1,2,3]
Key Contribution: We indicate for the first time the negative impact of DON on proliferation of the major porcine T-cell subsets and on the expression of the costimulatory molecules CD27 and CD28, which are essential for optimal T-cell activation and the subsequent survival and proliferation of activated T cells
Various in vitro studies conducted in the past have shown that DON can impair the survival of different cell types [32,33]; in this study we initially investigated the impact of DON and DOM-1 on porcine peripheral blood mononuclear cells (PBMCs) viability

Summary

Introduction

The Fusarium mycotoxin deoxynivalenol (DON) is a secondary fungal metabolite, which contaminates cereal-based foods worldwide and, is considered as a threat for public health and for the nutrition of farm animals [1,2,3]. Pigs are highly exposed to DON and other mycotoxins due to their cereal-rich diet, leading to health problems and impairment of performance traits [4,5]. DON induces a ribotoxic stress response via binding to the peptidyl transferase center of the 60S unit of the ribosome, which results in elongation inhibition [6,7]. The binding to the ribosome leads to the activation of mitogen-activated protein kinases (MAPKs), which are involved in processes such as cell growth, proliferation, and apoptosis. For cells of the adaptive immune system, i.e., B and T cells, proliferation is essential for the activation and differentiation of cells into effector and memory subsets. Previous studies have shown that DON impairs cell proliferation, including cells of the immune system [11,12,13].

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