Bovine Peripheral Blood Mononuclear Cells Are More Sensitive to Deoxynivalenol Than Those Derived from Poultry and Swine

Novak, Barbara; Springler, Alexandra; Pierron, Alix; Gerner, Wilhelm; Reisinger, Nicole; Hessenberger, Sabine; Schatzmayr, Gerd; Mayer, Eric

doi:10.3390/toxins10040152

Cited by 20 publications

(38 citation statements)

References 52 publications

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“…This suggests that DOM-1 has still some biological activity, at least at such high concentrations as used in our study. Next to these findings, Novak et al (4) mentioned that in the DOM-1 that was used in their in vitro experiments 0.1-0.2% impurities of DON were detected that could explain some of the immunomodulatory effects of the tested substance.…”

Section: Discussionmentioning

confidence: 98%

“…This frequently leads to health problems in this species ( 2 , 3 ). In vitro studies performed on porcine lymphocytes and other immune-related cells have shown that DON impairs the function of these cells, such as their survival, proliferation and maturation ( 4 – 7 ). In a recent study, we could show by flow cytometry (FCM) phenotyping that DON concentrations higher than 0.4 μM decrease the proliferation of major porcine T-cell subsets, namely CD4 + , CD8 + , and γδ T cells ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

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Deoxynivalenol Has the Capacity to Increase Transcription Factor Expression and Cytokine Production in Porcine T Cells

et al. 2020

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Deoxynivalenol (DON) is a Fusarium mycotoxin that frequently contaminates the feed of farm animals. Pigs with their monogastric digestive system are in particular sensitive to DON-contaminated feed. At high concentrations, DON causes acute toxic effects, whereas lower concentrations lead to more subtle changes in the metabolism. This applies in particular to the immune system, for which immunosuppressive but also immunostimulatory phenomena have been described. Research in human and rodent cell lines indicates that this may be partially explained by a binding of DON to the ribosome and subsequent influences on cell signaling molecules like mitogen-activated protein kinases. However, a detailed understanding of the influence of DON on functional traits of porcine immune cells is still lacking. In this study, we investigated the influence of DON on transcription factor expression and cytokine production within CD4 + , CD8 + , and γδ T cells in vitro. At a DON concentration, that already negatively affects proliferation after Concanavalin A stimulation (0.8 µM) an increase of T-bet expression in CD4 + and CD8 + T cells was observed. This increase in T-bet expression coincided with elevated levels of IFN-γ and TNF-α producing T-cell populations. Increases in T-bet expression and cytokine production were found in proliferating and non-proliferating T cells, although increases were more prominent in proliferating cell subsets. Differently, IL-17A production by CD4 + T cells was not influenced by DON. In addition, frequencies of regulatory T cells and their expression of Foxp3 were not affected. In γδ T cells, GATA-3 expression was slightly reduced by DON, whereas T-bet levels were only slightly modulated and hence IFN-γ, TNF-α, or IL-17A production were not affected. Our results show for the single-cell level that DON has the capacity to modulate the expression of transcription factors and related cytokines. In particular, they suggest that for CD4 + and CD8 + T cells, DON can drive T-cell differentiation into a pro-inflammatory type-1 direction, probably depending on the already prevailing cytokine milieu. This could have beneficial or detrimental effects in ongoing immune responses to infection or vaccination.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Deoxynivalenol Has the Capacity to Increase Transcription Factor Expression and Cytokine Production in Porcine T Cells

et al. 2020

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“…Both parameters were significantly affected by intrauterine exposure to DON. A significant impact of DON on T cells has previously been demonstrated in mice [ 46 , 47 ], cattle [ 48 , 49 ], poultry [ 49 ], and pigs [ 50 , 51 , 52 ]. In contrast, several studies of pigs have reported that long-term exposure to DON does not lead to any significant changes in the percentage of lymphocyte subpopulations [ 42 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

Maternal Exposure Results in Long-Term Deoxynivalenol Persistence in Piglets’ Plasma and Modulates the Immune System

Štěpánová

Hlavová

Šťastný

et al. 2020

Toxins

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Deoxynivalenol (DON)-contaminated feed represents a serious problem for pigs due to their high sensitivity to its toxicological effects. The aim of the present study was to evaluate the impact of intrauterine DON exposure on the immune system of piglets. Pure DON was intravenously administered to sows at the end of gestation (during the last 2–3 days of gestation, one dose of 300 µg per day). The plasma concentration of DON was analyzed using liquid chromatography combined with high-resolution Orbitrap-based mass spectrometry (LC–MS/MS (HR)) and selected immune parameters were monitored six times in piglets from birth to 18 weeks. DON was found in the plasma of 90% of newborn piglets at a mean concentration of 6.28 ng/mL and subsequently, at one, three, and seven weeks after birth with decreasing concentrations. Trace amounts were still present in the plasma 14 weeks after birth. Flow cytometry revealed a significant impact of DON on T lymphocyte subpopulations during the early postnatal period. Lower percentages of regulatory T cells, T helper lymphocytes, and their double positive CD4+CD8+ subset were followed by increased percentages of cytotoxic T lymphocytes and γδ T cells. The capacity to produce pro-inflammatory cytokines was also significantly lower after intrauterine DON exposure. In conclusion, this study revealed a long-term persistence of DON in the plasma of the piglets as a consequence of short-term intrauterine exposure, leading to altered immune parameters.

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“…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]. In the study by Novak et al [13], the influence of different DON and deepoxy-deoxynivalenol (DOM-1) concentrations on the proliferation of Concanavalin A (ConA)-stimulated bovine, porcine, and chicken peripheral blood mononuclear cells (PBMCs) was investigated.…”

Section: Introductionmentioning

confidence: 99%

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

Pierron

Saalmüller

Mayer³

et al. 2019

Toxins

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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.

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Bovine Peripheral Blood Mononuclear Cells Are More Sensitive to Deoxynivalenol Than Those Derived from Poultry and Swine

Cited by 20 publications

References 52 publications

Deoxynivalenol Has the Capacity to Increase Transcription Factor Expression and Cytokine Production in Porcine T Cells

Deoxynivalenol Has the Capacity to Increase Transcription Factor Expression and Cytokine Production in Porcine T Cells

Maternal Exposure Results in Long-Term Deoxynivalenol Persistence in Piglets’ Plasma and Modulates the Immune System

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

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