Effect of Mucosal Cytokine Administration on Selective Expansion of Vaginal Dendritic Cells to Support Nanoparticle Transport.
PROBLEM
The capacity of antigen-carrying vaccine nanoparticles (NPs) administered vaginally to stimulate local immune responses may be limited by the relatively low numbers of antigen-presenting cells (APCs) in the genital mucosa. Because inflammation is associated with increased susceptibility to sexually transmitted infections, we sought to increase APC numbers without causing inflammation.


METHOD OF STUDY
In this study, we evaluated intravaginal delivery of chemokines, growth factors, or synthetic adjuvants to expand APCs in reproductive tissues.


RESULTS
We found that granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulated expansion of CD11b+ dendritic cells (DCs) within 24 hr of intravaginal administration, with no effect on Langerhans cells or macrophages. Expansion of the CD11b+ DC population was not associated with increased inflammatory cytokine production, and these cells retained phagocytic function.


CONCLUSION
Our data suggest that non-inflammatory expansion of mucosal APCs by intravaginal GM-CSF could be used as an adjuvanting strategy to potentiate the genital immune response to nanoparticulate mucosal vaccines.
['Ramanathan|Renuka|R|', 'Park|Jaehyung|J|', 'Hughes|Sean M|SM|', 'Lykins|William R|WR|', 'Bennett|Hunter R|HR|', 'Hladik|Florian|F|', 'Woodrow|Kim A|KA|']
D000282:Administration, Intravaginal D000818:Animals D001692:Biological Transport D039481:CD11b Antigen D018925:Chemokines D005260:Female D016178:Granulocyte-Macrophage Colony-Stimulating Factor D007249:Inflammation D007801:Langerhans Cells D008264:Macrophages D051379:Mice D008810:Mice, Inbred C57BL D009092:Mucous Membrane D053758:Nanoparticles D014614:Vaccines, Synthetic D014621:Vagina
dendritic cells chemokines GM-CSF Cellular expansion reproductive mucosa