MucosaI immunity in the upper respiratory tract and vaccine development

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Dendritic cells (DCs) are essential for the induction of antigen (Ag)-specific immune responses, DC-targeted vaccination might be an effective strategy for the induction of the specific immune responses. Flt3 ligand (Flt3L) mobilizes and stimulates myeloid and lymphoid progenitor cells, and DCs. The purpose of this study is to investigate the effect of Flt3L on the induction of Ag-specific immune responses in nasal mucosa. Mice were administered with Flt3L 10Hg intranasally or intraperitoneally, on day 0. After the Flt3L application, mice were further immunized with P6 outer membrane protein of nontypeable Haemophilus influenzae (NTHi) 10μg on day 6, 13, and 20, and mice were killed on day 27. Control were not given Flt3L. The number and subset of DCs in nasal-associated lymphoid tissue (NALT) were analyzed by flow cytometry. P6-specific antibody titers in nasal wash and serum were measured by enzyme-linked immunosorbent assay (ELISA), and P6-specific antibody-producing cells were examined by enzyme-linked immunospot (ELISPOT) assay. CD11c^+ DCs increased in NALT after nasal Flt3L administration. In addition, P6-specific nasal IgA and systemic IgG titers were significantly elevated in nasally Flt3L-treated mice, possessing higher number of the specific IgA-producing in nasal mucosa. This study showed that nasal but not peritoneal application with a single dose of Flt3L induced increase of NALT DCs, resulted in enhanced local and systemic immune responses. These findings suggest that nasal application with Flt3L might be a useful vaccine strategy.