title: Epicutaneous immunization with protein antigen TNP-Ig and NOD2 ligand muramyl dipeptide (MDP) reverses skin-induced suppression of contact hypersensitivity.
abstract: BACKGROUND
  Epicutaneous (EC) immunization offers a new method of a needle-free and self-administrable immunization by using a topically applied patch to deliver vaccine. We have previously shown that EC immunization with hapten-conjugated protein antigen TNP-Ig prior to hapten sensitization inhibits Th1-mediated contact hypersensitivity (CHS) in mice. Our further work showed that EC immunization with TNP-Ig and Toll-like receptor (TLR) ligands prior to hapten sensitization reverses skin-induced suppression.
  
  
  METHODS
  Animal model of contact hypersensitivity was used to study reversal of skin-induced suppression.
  
  
  RESULTS
  Current work showed that EC immunization with protein antigen TNP-Ig and MDP NOD2 agonist - muramyldipeptide (L isoform) reverses skin-induced suppression of CHS. On the other hand L18-MDP NOD2 agonist - muramyldipeptide with a C18 fatty acid chain and MDP control - negative control for MDP - muramyldipeptide (D isoform, inactive) did not reverse skin-induced suppression. "Transfer in" experiment showed that reversal of skin-induced suppression can be adoptively transferred with lymphoid cells isolated from donors EC treated with TNP-Ig and MDP NOD2 agonist. Moreover, experiment employing two non-cross-reacting antigens TNP-Ig and OX-Ig proved that reversal of skin-induced suppression is antigen specific. Additionally, lymph node cells isolated from mice EC immunized with TNP-Ig and MDP NOD2 agonist produced increased level of IFN-γ suggesting that this cytokine might be involved in reversal of skin-induced suppression.
  
  
  CONCLUSIONS
  This work shows that EC immunization with protein antigen plus NOD2 ligand MDP may be a potential tool to increase the immunogenicity of weekly immunogenic antigens.
authors.affiliation: Department of Medical Biology, Jagiellonian University College of Medicine, Kraków, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Majewska-Szczepanik
authors.affiliation: Department of Medical Biology, Jagiellonian University College of Medicine, Kraków, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Dorożyńska
authors.affiliation: Department of Medical Biology, Jagiellonian University College of Medicine, Kraków, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Strzępa
authors.affiliation: Department of Medical Biology, Jagiellonian University College of Medicine, Kraków, Poland. Electronic address: mmszczep@cyf-kr.edu.pl.
authors.forename: Marian
authors.initials: M
authors.lastname: Szczepanik
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000276:immunology*; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D003877:Dermatitis, Contact / Q000517:prevention & control*; D007114:Immunization; D007136:Immunoglobulins / Q000276:immunology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D053473:Nod2 Signaling Adaptor Protein / Q000819:agonists*; D012867:Skin / Q000276:immunology*; D014301:Trinitrobenzenes / Q000276:immunology*
chemical_list: D016207:Cytokines; D007136:Immunoglobulins; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D014301:Trinitrobenzenes; D000119:Acetylmuramyl-Alanyl-Isoglutamine
keywords: Contrasuppression; Epicutaneous immunization; NOD-like receptors; Reversal of suppression