Although the strongest mucosal adjuvants are members of the family of HLTs, the inherent toxicities of HLT holotoxins preclude their clinical use. Herein, it is shown that LT-IIa-B(5) enhances mucosal immune responses by modulating activities of DCs. i.n. immunization of mice with OVA in the presence of LT-IIa-B(5) recruited DCs to the NALT and significantly increased uptake of OVA by those DCs. Furthermore, LT-IIa-B(5) increased expression of CCR7 by DCs, which mediated enhanced migration of the cells from the NALT to the draining CLNs. LT-IIa-B(5) also enhanced maturation of DCs, as revealed by increased surface expression of CD40, CD80, and CD86. Ag-specific CD4(+) T cell proliferation was augmented in the CLNs of mice that had received i.n. LT-IIa-B(5). Finally, when used as an i.n. adjuvant, LT-IIa-B(5) dramatically increased the levels of OVA-specific salivary IgA and OVA-specific serum IgG. Strikingly, each of the activities induced by LT-IIa-B(5) was strictly TLR2-dependent. The data strongly suggest that the immunomodulatory properties of LT-IIa-B(5) depend on the productive modulation of mucosal DCs. Notably, this is the first report for any HLT to demonstrate in vivo the elicitation of strong, TLR2-dependent modulatory effects on DCs with respect to adjuvanticity.
JournalJournal of leukocyte biology
J Leukoc Biol (1938-3673)
Department of Microbiology and Immunology, University at Buffalo, Buffalo, NY 14214, USA.
J Leukoc Biol. 2011 Nov;90(5):911-21
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