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

Abstract

Objectives: Thymosin α 1 (Tα1) 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 Tα1 would address in vitro the response of human primary monocyte-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 Tα1 on DC biology upon viral or bacterial stimulation. Interestingly, Tα1 enhanced human leukocyte antigen (HLA)-I and II surface expression and secretion of IL-6, TNF-α and IL-8 when DCs were treated with viral TLR3 and TLR7/8 agonists. Similarly, in pandemic H1N1 influenza A-infected DCs, Tα1 raised the expression of maturation markers and type I and III Interferon (IFN). In contrast, following bacterial TLR2 and 4 stimulation, as well as upon Bacillus Calmette–Guerin infection, the presence of Tα1 in DC cultures drastically lowered the analyzed cellular parameters.

Conclusion: The knowledge that Tα1 pleiotropic effect might ameliorate anti-viral 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.

Keywords:

• dendritic cell
• human
• Thymosin α 1
• toll-like receptor

Acknowledgments

E Giacomini & M Severa shared the first authorship. We thank Eugenio Morassi (Division Service for Data Management, Documentation, Library and Publishing Activities, Istituto Superiore di Sanità, Rome, Italy) for drawings. Work presented at the ‘4th International Symposium on Thymosins in Health & Disease,’ 23rd – 25th October, 2014 (Hotel Ripetta, Rome, Italy).

Declaration of interest

This paper is part of a supplemental issue, sponsored by SciClone. Our work was supported in part by grant RF-2010235199 from Italian Ministry of Health and from Istituto Superiore di Sanità (to EMC). EG is a Thymosin patent holder. EMC is the PI of a sponsored research agreement between Istituto Superiore di Sanità and Novartis Vaccines and Diagnostics s.r.l. The other authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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