title: Dual effect of Thymosin α 1 on human monocyte-derived dendritic cell in vitro stimulated with viral and bacterial toll-like receptor agonists.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Istituto Superiore di Sanità of Infectious, Parasitic and Immune-mediated Diseases, Viale Regina Elena, Rome, 00151 , Italy +39 06 49903638 ; +39 06 49903638 ; eliana.coccia@iss.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Giacomini
authors.forename: Martina
authors.initials: M
authors.lastname: Severa
authors.forename: Melania
authors.initials: M
authors.lastname: Cruciani
authors.forename: Marilena Paola
authors.initials: MP
authors.lastname: Etna
authors.forename: Fabiana
authors.initials: F
authors.lastname: Rizzo
authors.forename: Manuela
authors.initials: M
authors.lastname: Pardini
authors.forename: Carolina
authors.initials: C
authors.lastname: Scagnolari
authors.forename: Enrico
authors.initials: E
authors.lastname: Garaci
authors.forename: Eliana Marina
authors.initials: EM
authors.lastname: Coccia
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D009163:Mycobacterium bovis; D013601:T-Lymphocytes / Q000276:immunology; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051193:Toll-Like Receptors / Q000819:agonists* / Q000276:immunology
chemical_list: D016207:Cytokines; D051193:Toll-Like Receptors; D013947:Thymosin; D000077596:Thymalfasin
keywords: Thymosin α 1; dendritic cell; human; toll-like receptor