Environmentally relevant dose of arsenic interferes in functions of human monocytes derived dendritic cells

• Published in: Toxicology letters Vol. 275; pp. 118 - 122
• Main Authors: Bahari, Abbas, Salmani, Vahid
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05-06-2017
• Subjects: Adolescent; Apoptosis - drug effects; Arsenic; Arsenic - toxicity; Cell Survival - drug effects; Cells, Cultured; Cytokines - genetics; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - pathology; Dose-Response Relationship, Drug; Environmental Pollutants - toxicity; Flow Cytometry; Humans; Leukocytes, Mononuclear - cytology; Male; Monocytes derived dendritic cells; Phagocytosis; Phagocytosis - drug effects; Proinflammatory cytokines; Transcriptome - drug effects; Young Adult; Monocytes derived dendritic cells; Proinflammatory cytokines; Arsenic; Phagocytosis
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2017.05.005

•Low doses of arsenic dramatically decreases phagocytosis capacity of MDDCs through the down-regulation of MHCII and CD40.•Arsenic exposure differently and TLRs-independently changes genes expression of pro-inflammatory cytokines.•Only one ppb arsenic turns MDDCs to apoptotic but not necrotic state.
Arsenic is a major environmental pollutant and highly hazardous toxin to human health, which well established as carcinogen and immune deregulatory properties. Dendritic cells (DCs) have a pivotal role in cell-mediated immunity for T-cell activation and antigen presentation.
In this study, T cell activation, some key functional genes expression, cell stability and phagocytosis capacity of human monocytes derived DCs (MDDCs) were analyzed after in vitro exposure to very low dose of arsenic for 12 and 24h. Arsenic decreased continually phagocytosis capacity of MDDCs. Furthermore, down-regulation of the cell-surface expression of the co-stimulatory molecule CD40 after 24h post treatment with arsenic, confirmed arsenic interferers in the phagocytosis process. Pro inflammatory cytokines, IL1β and TNFα were more expressed in arsenic-treated MDDCs while IL6 transiently was down regulated.
In general, our novel findings here strongly suggest that low level of arsenic dysregulates four fundamental immune processes of DCs. Mechanistically; this could explain the observed immunodeficiency activity of Arsenic, and give direction for comprehension the pathogenesis of Arsenic-induced diseases.