Abstract
Cytotoxic necrotizing factor 1 (CNF1) from uropathogenic Escherichia coli belongs to a family of factors activating Rho GTPases. We report the in vivo effects of CNF1 in mice co-fed toxin and the soluble protein antigen ovalbumin (OVA). Similar to cholera toxin, CNF1 elicits adjuvanticity anti-OVA responses, both systemic and mucosal. In contrast, the catalytic inactive mutant CNF1-C866S demonstrated no effects. Using dermonecrotic toxin (DNT), a closely related Rho activating toxin from Bordetella, we discovered that the adjuvant property is within the DNT catalytic domain. Manipulation of Rho proteins thus provides a possible new approach for the development of effective mucosal immunoadjuvants.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic*
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Animals
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Antibody Formation / drug effects
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Bacterial Toxins / genetics
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Bacterial Toxins / pharmacology*
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Enzyme Activation
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Enzyme-Linked Immunosorbent Assay
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Escherichia coli Proteins / genetics
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Escherichia coli Proteins / pharmacology*
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Female
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Immunity, Mucosal / drug effects*
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Immunization
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Mice
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Mice, Inbred BALB C
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Ovalbumin / immunology
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Transglutaminases / genetics
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Transglutaminases / pharmacology*
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Virulence Factors, Bordetella / genetics
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Virulence Factors, Bordetella / pharmacology*
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rho GTP-Binding Proteins / metabolism*
Substances
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Adjuvants, Immunologic
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Bacterial Toxins
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Escherichia coli Proteins
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Virulence Factors, Bordetella
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dermonecrotic toxin, Bordetella
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cytotoxic necrotizing factor type 1
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Ovalbumin
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Transglutaminases
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rho GTP-Binding Proteins