INDUCTION OF PROTECTIVE IMMUNITY AFTER ESCHERICHIA-COLI BLADDER INFECTION IN PRIMATES - DEPENDENCE OF THE GLOBOSIDE-SPECIFIC P-FIMBRIAL TIPADHESIN AND ITS COGNATE RECEPTOR

Clinical observations suggest that immune mechanisms affect etiology a nd course of recurrent cystitis, A primate infection model was used to show that primary bladder infection with a uropathogenic P-fimbriated strain (binding to globoside present in the bladder wall) protects ag ainst rechallenge with homologous as well as heterologous Escherichia coli strains for up to 5-6 mo. In contrast, mutant derivatives produci ng P-fimbriae either lacking the tip adhesin protein or carrying an ad hesin for which no bladder receptor was present, were unable to induce protection, even though they generated bladder infections of similar duration as the wild type. Therefore, the protective effect mediated b y the adhesin seemed to depend upon the presence of its cognate recept or, Since the wild strain also mediated protection against mutants tha t lacked the adhesin, our data suggest that the globoside-binding PapG adhesin acts as an adjuvant during infection to enhance a specific re sponse against other bacterial antigens. In fact, the globoside-bindin g strain DS17, but not the mutant DS17-1, unable to bind to membrane-b ound globoside, elicited a secretory IgA response to LPS in urine, The se in vivo findings suggest that bacterial adhesin-ligand interactions may have signaling functions of importance for the immune response.