Nanoemulsion mucosal adjuvant uniquely activates cytokine production by nasal ciliated epithelium and induces dendritic cell trafficking.
While the nasal mucosa is a potentially useful site for human immunization, toxin-based nasal adjuvants are generally unsafe and less effective in humans. Safe mucosal adjuvants that activate protective immunity via mucosal administration are highly dependent on barrier antigen sampling by epithelial and DCs. Here, we demonstrate that protein antigens formulated in unique oil-in-water nanoemulsions (NEs) result in distinctive transcellular antigen uptake in ciliated nasal epithelial cells, leading to delivery into nasal associated lymphoid tissue. NE formulation also enhances MHC class II expression in epithelial cells and DC activation/trafficking to regional lymphoid tissues in mice. These materials appear to induce local epithelial cell apoptosis and heterogeneous cytokine production by mucosal epithelial cells and mixed nasal tissues, including G-CSF, GM-CSF, IL-1a, IL-1b, IL-5, IL-6, IL-12, IP-10, KC, MIP-1a, TGF-β, and TSLP. This is the first observation of a nasal adjuvant that activates calreticulin-associated apoptosis of ciliated nasal epithelial cells to generate broad cytokine/chemokine responses in mucosal tissue.
Division of Allergy and Clinical Immunology, Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA. pmakidon@umich.edu
Paul E
PE
Makidon
Igor M
IM
Belyakov
Luz P
LP
Blanco
Katarzyna W
KW
Janczak
Jeffrey
J
Landers
Anna U
AU
Bielinska
Jeffrey V
JV
Groom
James R
JR
Baker
D000276:Adjuvants, Immunologic; D000818:Animals; D017209:Apoptosis; D001692:Biological Transport / Q000276:immunology; D037282:Calreticulin; D002465:Cell Movement; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004655:Emulsions; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005802:Genes, MHC Class II; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009297:Nasal Mucosa / Q000276:immunology* / Q000378:metabolism
D000276:Adjuvants, Immunologic; D037282:Calreticulin; D016207:Cytokines; D004655:Emulsions; D015850:Interleukin-6