title: Exposure to nicotine adversely affects the dendritic cell system and compromises host response to vaccination.
abstract: The magnitude of Th1 cells response to vaccination is a critical factor in determining protection from clinical disease. Our previous in vitro studies suggested that exposure to the nicotine component of cigarette smoke skews the differentiation of both human and mouse dendritic cell (DC) precursors into atypical DCs (DCs differentiated ex vivo in the presence of nicotine) lacking parameters essential for the development of Th1-mediated immunity. In this study, we determined the causal relationship between nicotine-induced DC alterations and host response to vaccines. We show that animals exposed to nicotine failed to develop and maintain Ag-specific effector memory Th1 cells and Ab production to protein-based vaccine formulated with Th1 adjuvants. Accordingly, both prophylactic and therapeutic vaccines failed to protect and cure the nicotine-exposed mice from disease. More importantly, we demonstrate the nicotine-induced defects in the biological activities of in vivo DCs as an underlying mechanism. Indeed, i.v. administration of DCs differentiated in the presence of nicotine preferentially promoted the development of Ag-specific IL-4-producing effector cells in the challenged mice. In addition, DC subsets isolated from mice exposed to nicotine produced significantly less cytokines in response to Th1 adjuvants and inadequately supported the development of Ag-specific Th1 cells. Collectively, our studies suggest that nicotine-induced defects in the DC system compromises vaccine efficacy in smokers.
authors.affiliation: Clinical Biomedical Science Department, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL 33431, USA. mahyar.shirazi@fau.edu
authors.forename: Mahyar
authors.initials: M
authors.lastname: Nouri-Shirazi
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Guinet
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009538:Nicotine / Q000633:toxicity*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000637:transplantation; D014611:Vaccination / Q000009:adverse effects* / Q000379:methods
chemical_list: D018984:Epitopes, T-Lymphocyte; D009538:Nicotine; D010047:Ovalbumin