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Hum Vaccin Immunother. 2014;10(8):2328-35. doi: 10.4161/hv.29520.

Thimerosal compromises human dendritic cell maturation, IL-12 production, chemokine release, and T-helper polarization.

Author information

1
a Institut Pasteur; Antiviral Immunity Biotherapy and Vaccine Unit; Infection and Epidemiology Department; Paris, France.

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.

KEYWORDS:

Th polarization; chemokines; cytokines; dendritic cells; thimerosal

PMID:
25424939
PMCID:
PMC4896785
DOI:
10.4161/hv.29520
[Indexed for MEDLINE]
Free PMC Article

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