Main content area

High dosage of zinc modulates T-cells in a time-dependent manner within porcine gut-associated lymphatic tissue

Kreuzer-Redmer, Susanne, Arends, Danny, Schulte, Jasper N., Karweina, Diana, Korkuc, Paula, Wöltje, Nadine, Hesse, Deike, Pieper, Robert, Gerdts, Volker, Zentek, Jürgen, Meurens, Francois, Brockmann, Gudrun A.
The British journal of nutrition 2018 v.120 no.12 pp. 1349-1358
CD4-positive T-lymphocytes, adaptive immunity, cytokines, diarrhea, diet, feed additives, genes, immune response, interferon-gamma, lymphatic system, piglets, zinc
Zn serves as a powerful feed additive to reduce post-weaning diarrhoea in pigs. However, the mechanisms responsible for Zn-associated effects on the adaptive immune responses following feeding of a very high dosage of Zn remain elusive. In this study, we examined the T-cell response in gut-associated lymphatic tissues of seventy-two weaned piglets. Piglets received diets with 57 mg Zn/kg (low Zn concentration, LZn), 164 mg Zn/kg (medium Zn concentration, MZn) or 2425 mg Zn/kg (high Zn concentration, HZn) mg Zn/kg feed for 1, 2 or 4 weeks. We observed that feeding the HZn diet for 1 week increased the level of activated T-helper cells (CD4⁺ and CD8α ᵈⁱᵐ) compared with feeding MZn and LZn (P<0·05). In addition, we observed higher transcript amounts of interferon γ and T-box 21 (TBET) in the HZn group compared with the MZn and LZn groups (P<0·05). A gene set enrichment analysis revealed an over-representation of genes associated with ‘cytokine signalling in immune system’. Remarkably, feeding of a very high Zn dosage led to a switch in the immune response after 2 weeks. We detected higher relative cell counts of CD4⁺CD25ʰⁱᵍʰ regulatory T-helper cells (P<0·05) and a higher expression of forkhead box P3 (FOXP3) transcripts (P<0·05). After 4 weeks of feeding a high-dosage Zn diet, the relative CD4⁺ T-cell count (P<0·05) and the relative CD8β ⁺ T-cell count (P<0·1) were reduced compared with the MZn group. We hypothesise that after 1 week the cellular T-helper 1 response is switched on and after 2 weeks it is switched off, leading to decreased numbers of T-cells.