Dual effect of Thymosin α 1 on human monocyte-derived dendritic cell in vitro stimulated with viral and bacterial toll-like receptor agonists

Objectives: Thymosin a 1 (T alpha 1) recently gained interest as immune adjuvant for vaccines because of its ability to modulate the T-cell/dendritic cell (DC) axis and to improve antibody production. The objective of this study was to determine whether T alpha 1 would address in vitro the response of human primary nnonocyte-derived DC, crucial regulators of vaccine-induced immunity, upon exposure to different toll-like receptor (TLR) agonists or infection with viruses or bacteria. Methods: DC maturation and production of pro-inflammatory cytokines were analyzed. Results: Our data revealed a dual effect of T alpha 1 on DC biology upon viral or bacterial stimulation. Interestingly, T alpha 1 enhanced human leukocyte antigen (HLA)-I and II surface expression and secretion of IL-6, TNF-alpha and IL-8 when DCs were treated with viral TLR3 and TLR7/8 agonists. Similarly, in pandemic H1N1 influenza A-infected DCs, T alpha 1 raised the expression of maturation markers and type I and Ill Interferon (IFN). In contrast, following bacterial TLR2 and 4 stimulation, as well as upon Bacillus Calmette-Guerin infection, the presence of T alpha 1 in DC cultures drastically lowered the analyzed cellular parameters. Conclusion: The knowledge that T alpha 1 pleiotropic effect might ameliorate antiviral immune responses and, at the same time, dampen inflammation caused by bacterial infections could lay the groundwork for a more appropriate therapeutic application of this molecule.