Interleukin 12 and innate molecules for enhanced mucosal immunity

Recent strategies for understanding the mechanisms underlying mucosal immun e responses and subsequent development of mucosal vaccines for induction of targeted immunity now include cytokines and molecules of innate immunity. These studies have shown that cytokines influencing the development of T he lper (Th) cells differentially affect the outcome of mucosal vs systemic im mune responses to mucosal vaccines. Serum antigen-specific antibody (Ab) re sponses were enhanced when either IL-6 or IL-12 was mucosally administered with a protein antigen, while only IL-12 induced antigen-specific mucosal I gA Ab responses. Mucosal IL-6 and IL-12 also affected the type of Th cell r esponses induced by CD4(+) T cells from mice that received IL-12 secreted l arger amounts of IFN-gamma and IL-6 when compared with mice nasally treated with IL-6. Discrepancies in the ability to enhance mucosal or systemic imm une responses were also observed when human neutrophil peptide (HNP) defens ins or lymphotactin were nasally coadministered with protein antigens. Only lymphotactin promoted mucosal secretory IgA (S-IgA) Ab responses while bot h lymphotactin and defensins enhanced systemic immunity to mucosally co-adm inistered protein antigens. Mixed antigen-specific Th1- and Th2-type CD4(+) T cell responses were induced in the systemic compartment by both lymphota ctin and the mixture of HNP-1, HNP-2, and HNP-3 defensins. However, HNPs fa iled to significantly enhance cytokine secretion by mucosally derived, anti gen-specific CD4+ T cells relative to those isolated from the systemic comp artment. In summary, these studies clearly show that IL-12 and lymphotactin are able to trigger S-IgA Ab responses and provide new avenues for the des ign of safe and targeted mucosal vaccines.