![]() ![]() Yet, endogenous cellular and molecular mechanisms in these mucosae commonly down-regulate mucosal immune responses to foreign Ag, likely as a means of avoiding elicitation of immune responses to the plethora of harmless Ags that are routinely encountered by the mucosae. The importance of these systems to human life is reflected in the observation that ∼80% of all immune cells in a healthy adult human are found in the various inductive and effector sites of the gut, respiratory, nasal, and other mucosae. To protect against these mucosal pathogens, humans evolved highly specialized innate and adaptive mucosal immune systems. 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.Ī majority of human pathogens invaded and/or colonized mucosal surfaces. The data strongly suggest that the immunomodulatory properties of LT-IIa-B 5 depend on the productive modulation of mucosal DCs. Strikingly, each of the activities induced by LT-IIa-B 5 was strictly TLR2-dependent. adjuvant, LT-IIa-B 5 dramatically increased the levels of OVA-specific salivary IgA and OVA-specific serum IgG. ![]() Ag-specific CD4 + T cell proliferation was augmented in the CLNs of mice that had received i.n. LT-IIa-B 5 also enhanced maturation of DCs, as revealed by increased surface expression of CD40, CD80, and CD86. 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. 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. Herein, it is shown that LT-IIa-B 5 enhances mucosal immune responses by modulating activities of DCs. Although the strongest mucosal adjuvants are members of the family of HLTs, the inherent toxicities of HLT holotoxins preclude their clinical use. Yet, strong, protective mucosal immune responses directed against those pathogens routinely cannot be induced without the use of adjuvants. ![]() A host of human pathogens invades the body at mucosal surfaces. ![]()
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