title: Vector-encoded Helicobacter pylori neutrophil-activating protein promotes maturation of dendritic cells with Th1 polarization and improved migration.
abstract: Helicobacter pylori neutrophil-activating protein (HP-NAP) is a major virulence factor involved in H. pylori infection. Both HP-NAP protein and oncolytic viruses encoding HP-NAP have been suggested as immunotherapeutic anticancer agents and adjuvants for vaccination but with little known about its mode of action to activate adaptive immunity. Dendritic cells (DCs) are key players in bridging innate and adaptive immune responses, and in this study we aim to evaluate the effect of HP-NAP on DC maturation, migration, and induction of adaptive immune response. Maturation markers CD83, CD80, CD86, HLA-DR, CD40, and CCR7 were upregulated on human DCs after treatment with supernatants from HP-NAP adenovirus-infected cells. HP-NAP-activated DCs had a Th1 cytokine secretion profile, with high IL-12 and relatively low IL-10 secretion, and migrated toward CCL19. Ag-specific T cells were efficiently expanded by Ag-presenting HP-NAP-activated DCs, which is an important property of functionally mature DCs. Furthermore, intradermal injections of HP-NAP-encoding adenovirus in C57BL/6 mice enhanced resident DC migration to draining lymph nodes, which was verified by imaging lymph nodes by two-photon microscopy and by phenotyping migrating cells by flow cytometry. In conclusion, therapeutic effects of HP-NAP are mediated by maturation of DCs and subsequent activation of Ag-specific T cells in addition to provoking innate immunity.
authors: Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, SE-75185 Uppsala, Sweden.
authors: Mohanraj
authors: M
authors: Ramachandran
authors: Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, SE-75185 Uppsala, Sweden.
authors: Chuan
authors: C
authors: Jin
authors: Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, SE-75185 Uppsala, Sweden.
authors: Di
authors: D
authors: Yu
authors: Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, SE-75185 Uppsala, Sweden.
authors: Fredrik
authors: F
authors: Eriksson
authors: Department of Immunology, Genetics, and Pathology, Science for Life Laboratory, Uppsala University, SE-75185 Uppsala, Sweden magnus.essand@igp.uu.se.
authors: Magnus
authors: M
authors: Essand
mesh_terms: D000256:Adenoviridae; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005822:Genetic Vectors; D016480:Helicobacter pylori / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D051379:Mice; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*
chemical_list: D000943:Antigens, Differentiation; D001426:Bacterial Proteins; C508609:IL10 protein, human; C556062:IL10 protein, mouse; D016753:Interleukin-10; D018664:Interleukin-12