The Rho GTPase activators CNF1 and DNT bacterial toxins have mucosal adjuvant properties.
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.
Munro
Patrick
P
INSERM, U627, Faculté de Médecine, 28 Avenue de Valombrose, F-06107 Nice Cedex 2, France.
Flatau
Gilles
G
Anjuère
Fabienne
F
Hofman
Véronique
V
Czerkinsky
Cecil
C
Lemichez
Emmanuel
E
D000276:Adjuvants, Immunologic; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001427:Bacterial Toxins / Q000235:genetics / Q000494:pharmacology*; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D029968:Escherichia coli Proteins / Q000235:genetics / Q000494:pharmacology*; D005260:Female; D018928:Immunity, Mucosal / Q000187:drug effects*; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D011503:Transglutaminases / Q000235:genetics / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000235:genetics / Q000494:pharmacology*; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D010566:Virulence Factors, Bordetella; C060969:dermonecrotic toxin, Bordetella; C060296:cytotoxic necrotizing factor type 1; D010047:Ovalbumin; D011503:Transglutaminases; D020741:rho GTP-Binding Proteins