Nicotine alters the biological activities of developing mouse bone marrow-derived dendritic cells (DCs).
Cigarette smoke contains nicotine, an immunomodulatory component that is thought to affect immune surveillance and increase the progression of diseases. Dendritic cells (DCs) constitute a family of antigen-presenting (APCs) with inherent abilities to sense and translate environmental cues and to shape host immunity. We recently reported on the effects of nicotine on human DCs and proposed a possible mechanism that links cigarette smoke to higher incidences of respiratory tract infection and asthma. To establish the causal relationship between nicotine-induced DC alterations and immunomodulation in vivo, we translated our in vitro human results to the mouse system and studied the direct effects of nicotine exposure on the biological and functional properties of mouse bone marrow (BM) DCs differentiated in vitro from their precursors. We report that while the presence of nicotine in the microenvironment has no direct effect on competent mouse BM-derived DCs function, it promotes the development of mouse BM DC precursors into DCs (thereafter called nicDCs) with a semi-mature phenotype revealed by higher expression of costimulatory molecules CD80, CD86, CD40, MHC II molecules and the lymph node homing receptor, CCR7. Consistent with their maturational status, these nicDCs have reduced capacity for antigen uptake and produce substantially less Th1-promoting cytokine, IL-12, in response to Th1-polarizing adjuvant, lipopolysaccharide (LPS). Interestingly, we found that nicDCs preferentially support the proliferation and differentiation of ovalbumin (OVA)-specific naïve T cells into effector memory cells, producing significantly less IFN-gamma and more IL-4. These results provide evidence for the similarity in the effects of nicotine on mouse and human DCs, particularly the ability to modulate DC differentiation towards developing Th2 immunity.
Nouri-Shirazi
M
M
Department of Biomedical Sciences, Immunology Laboratory, Texas A&M University System Health Science Center, Baylor College of Dentistry, Dallas, TX 75246, USA. mnshirazi@bcd.tamhsc.edu
Tinajero
R
R
Guinet
E
E
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D003911:Dextrans / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009538:Nicotine / Q000494:pharmacology*; D010047:Ovalbumin / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D003911:Dextrans; C015219:fluorescein isothiocyanate dextran; D009538:Nicotine; D010047:Ovalbumin; D016650:Fluorescein-5-isothiocyanate