title: Pidotimod promotes functional maturation of dendritic cells and displays adjuvant properties at the nasal mucosa level.
abstract: Mucosal dendritic cells (DCs) are very important in the process of antigen presentation to T cells, playing a key role in the induction of primary and secondary immune responses. Pidotimod is a synthetic substance capable of modulating immune cell functions, but the effect of pidotimod on human DCs has not been investigated yet. Here we demonstrate the ability of pidotimod to induce DC maturation and up-regulate the expression of HLA-DR and co-stimulatory molecules CD83 and CD86, which are fundamental for communication with adaptative immunity cells. Pidotimod also stimulated DCs to release high amounts of pro-inflammatory molecules such as MCP-1 and TNF-alpha cytokines and to drive T cell proliferation and differentiation towards a Th1 phenotype. Moreover, we demonstrate that pidotimod in vivo promotes strong and specific humoral and cellular immune response when co-administered intranasally with a model antigen. Taken together our data suggest the possibility to use pidotimod as adjuvant molecule to facilitate the activation of the innate immune system as well as to promote an effective mucosal and systemic immune response.
authors.affiliation: Department of Experimental and Applied Medicine, Section of Microbiology, University of Brescia, Medical School, Brescia, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Giagulli
authors.forename: Miriam
authors.initials: M
authors.lastname: Noerder
authors.forename: Manuela
authors.initials: M
authors.lastname: Avolio
authors.forename: Pablo D
authors.initials: PD
authors.lastname: Becker
authors.forename: Simona
authors.initials: S
authors.lastname: Fiorentini
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Guzman
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Caruso
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009297:Nasal Mucosa / Q000276:immunology* / Q000473:pathology; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D053778:Thiazolidines / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D006684:HLA-DR Antigens; D010446:Peptide Fragments; D053778:Thiazolidines; D014409:Tumor Necrosis Factor-alpha; C064893:pidotimod; D010047:Ovalbumin; D011761:Pyrrolidonecarboxylic Acid