Effect of Mucosal Cytokine Administration on Selective Expansion of Vaginal Dendritic Cells to Support Nanoparticle Transport. (27th June 2015)

• Record Type: Journal Article
• Authors: Ramanathan, Renuka; Park, Jaehyung; Hughes, Sean M.; Lykins, William R.; Bennett, Hunter R.; Hladik, Florian; Woodrow, Kim A.
• Is Part Of: American journal of reproductive immunology. Volume 74:Number 4(2015:Oct.)
• Page Start: 333
• Page End: 344
• Publication Date: 2015-06-27
• Subjects: Cellular expansion -- chemokines -- dendritic cells -- GM‐CSF -- reproductive mucosa; Human reproduction -- Immunological aspects -- Periodicals; 616.69206
• DOI: 10.1111/aji.12409
• Languages: English
• ISSNs: 1046-7408

Abstract

Abstract : 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.