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In vivo and in vitro adjuvant activities of the B subunit of Type IIb heat-labile enterotoxin (LT-IIb-B5) from Escherichia coli
Authors:Shuang Liang  Kavita B Hosur  Hesham F Nawar  Michael W Russell  Terry D Connell  George Hajishengallis
Institution:1. Department of Periodontics/Oral Health and Systemic Disease, University of Louisville School of Dentistry, Louisville, KY 40292, USA;2. Department of Microbiology and Immunology, Witebsky Center for Microbial Pathogenesis and Immunology, University at Buffalo, NY 14214, USA;3. Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40292, USA
Abstract:The pentameric B subunit of the Escherichia coli LT-IIb enterotoxin (LT-IIb-B5) activates TLR2 signaling in macrophages. Herein we demonstrate that LT-IIb-B5, in contrast to a TLR2-nonbinding point mutant, induces functional activation of bone marrow-derived dendritic cells and stimulates CD4+ T cell proliferation, activities which suggested that LT-IIb-B5 might function as an adjuvant in vivo. Indeed, in an intranasal mouse immunization model, LT-IIb-B5 augmented specific mucosal and serum antibody responses to a co-administered immunogen, at levels which were almost comparable to those induced by intact LT-IIb holotoxin, a potent but toxic adjuvant. Therefore, LT-IIb-B5 displays useful adjuvant properties which, combined with lack of enterotoxicity and relative stability against degradation, may find application in mucosal vaccines.
Keywords:Heat-labile enterotoxins  Mucosal adjuvants  Dendritic cells
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