Cadmium and wild boar: Environmental exposure and immunological impact on macrophages

Giulia Franzoni; Valentina Ciccotelli; Lucia Masiello; Chiara Grazia De Ciucis; Antonio Giovanni Anfossi; Barbara Vivaldi; Mauro Ledda; Susanna Zinellu; Silvia Dei Giudici; Enrica Berio; Andreoli Tiziana; Monica Dellepiane; Simona Zoppi; Chiara Masotti; Maria Ines Crescio; Annalisa Oggiano; Carlo Ercolini; Elisabetta Razzuoli

doi:10.1016/j.toxrep.2022.01.009

Cadmium and wild boar: Environmental exposure and immunological impact on macrophages

Toxicol Rep. 2022 Jan 29:9:171-180. doi: 10.1016/j.toxrep.2022.01.009. eCollection 2022.

Authors

Giulia Franzoni¹, Valentina Ciccotelli², Lucia Masiello², Chiara Grazia De Ciucis², Antonio Giovanni Anfossi^{3

4}, Barbara Vivaldi², Mauro Ledda³, Susanna Zinellu¹, Silvia Dei Giudici¹, Enrica Berio⁵, Andreoli Tiziana⁶, Monica Dellepiane⁶, Simona Zoppi⁷, Chiara Masotti⁷, Maria Ines Crescio⁸, Annalisa Oggiano¹, Carlo Ercolini², Elisabetta Razzuoli²

Affiliations

¹ Department of Animal Health, Istituto Zooprofilattico Sperimentale della Sardegna, Via Vienna 2, 07100 Sassari, Italy.
² National Reference Center of Veterinary and Comparative Oncology (CEROVEC), Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, Piazza Borgo Pila 39-24, 16129 Genova, Italy.
³ Department of Veterinary Medicine, University of Sassari, Via Vienna, 07100 Sassari, Italy.
⁴ Mediterranean Center for Disease Control (MCDC), University of Sassari, Via Vienna, 07100 Sassari, Italy.
⁵ Department of Imperia, Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, Via Nizza 4, 18100 Imperia, Italy.
⁶ Department of Savona, Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, Via Martini 6, 17100 Savona, Italy.
⁷ Laboratory of Veterinary Pathology, Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, Via Bologna 148, 10154 Torino, Italy.
⁸ Biostatistics, Epidemiology and Risk Analysis, Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, Via Bologna 148, 10154 Torino, Italy.

Abstract

Cadmium (Cd²⁺) is regarded as one of the most toxic heavy metals, which can enter the food chain through environmental contamination and be bioaccumulated. Its exposure in Ligurian wild boars was monitored between 2016-2020 and revealed high level of this heavy metal in different provinces. In one of these polluted area, 21 wild boars were additionally sampled and the relationship between hepatic and renal Cd²⁺ concentration suggested that majority of these animals presented chronic intoxication. Cd²⁺ exposure of wild boar might lead to an immunosuppression status, thus in vitro experiments on wild boar monocyte-derived macrophages (moMФ) were carried out. Effects of Cd²⁺ scalar doses were evaluated through viability and adsorption assays, ELISA, qPCR. Moderate doses of this environmental pollutant (20 μM) were absorbed by moMФ, with subsequent reduction of their viability. This heavy metal did not trigger release of either IFN- β, anti-inflammatory or pro-inflammatory cytokines by moMФ, instead 24 h treatment with 20 μM of Cd²⁺ resulted in down-regulated expression of TNF-α, IL-12p40, several TLRs, CD14, MD2, BD2, MyD88, p65, and NOS2. The results of our monitoring activity suggested that wild boar can be useful to monitor environmental exposure of this heavy metal and can help in understanding the type of contamination. In addition, in vitro experiments on wild boar moMФ revealed that Cd²⁺ exposure negatively affected the immune function of these cells, likely leading to increased susceptibility to infection.

Keywords: Antimicrobial molecules; Arg-1, arginase 1; BD, beta defensin; Cadmium; Cd2+, cadmium; Cytokines; Environmental contamination; IFN, Interferon; IL, Interleukin; LDH, lactate dehydrogenase; LPS, lipopolysaccharide; MD2, myeloid differentiation protein 2; Monocyte-derived macrophages; MyD88, myeloid differentiation factor 88; NOS2, nitric oxide synthase 2; PAMPs, pathogen associated molecular patterns; TLR, Toll-like receptor; TLRs; TNF, tumor necrosis factor; Wild boars; iNOS, inducible nitric oxide synthase; moMФ, monocyte-derived macrophages.