title: Thimerosal compromises human dendritic cell maturation, IL-12 production, chemokine release, and T-helper polarization.
abstract: Thimerosal is a preservative used in multidose vials of vaccine formulations to prevent bacterial and fungal contamination. We recently reported that nanomolar concentrations of thimerosal induce cell cycle arrest of human T cells activated via the TCR and inhibition of proinflammatory cytokine production, thus interfering with T-cell functions. Given the essential role of dendritic cells (DCs) in T-cell polarization and vaccine immunity, we studied the influence of non-toxic concentrations of thimerosal on DC maturation and functions. Ex-vivo exposure of human monocyte-derived DCs to nanomolar concentrations of thimerosal prevented LPS-induced DC maturation, as evidenced by the inhibition of morphological changes and a decreased expression of the maturation markers CD86 and HLA-DR. In addition thimerosal dampened their proinflammatory response, in particular the production of the Th1 polarizing cytokine IL-12, as well as TNF-α and IL-6. DC-dependent T helper polarization was altered, leading to a decreased production of IFN-γ IP10 and GM-CSF and increased levels of IL-8, IL-9, and MIP-1α. Although multi-dose vials of vaccines containing thimerosal remain important for vaccine delivery, our results alert about the ex-vivo immunomodulatory effects of thimerosal on DCs, a key player for the induction of an adaptive response.
authors.affiliation: a Institut Pasteur; Antiviral Immunity Biotherapy and Vaccine Unit; Infection and Epidemiology Department; Paris, France.
authors.forename: Emily
authors.initials: E
authors.lastname: Loison
authors.forename: Marie-Lise
authors.initials: ML
authors.lastname: Gougeon
mesh_terms: D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism*; D011310:Preservatives, Pharmaceutical / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013849:Thimerosal / Q000378:metabolism*
chemical_list: D018925:Chemokines; D007155:Immunologic Factors; D011310:Preservatives, Pharmaceutical; D018664:Interleukin-12; D013849:Thimerosal
keywords: Th polarization; chemokines; cytokines; dendritic cells; thimerosal