title: CD40 Ligand Deficient C57BL/6 Mouse Is a Potential Surrogate Model of Human X-Linked Hyper IgM (X-HIGM) Syndrome for Characterizing Immune Responses against Pathogens.
abstract: Individuals with X-HIGM syndrome fail to express functional CD40 ligand; consequently they cannot mount effective protective antibody responses against pathogenic bacteria. We evaluated, compared, and characterized the humoral immune response of wild type (WT) and C57-CD40L deficient (C57-CD40L(-/-)) mice infected with Citrobacter rodentium. Basal serum isotype levels were similar for IgM and IgG3 among mice, while total IgG and IgG2b concentrations were significantly lower in C57-CD40L(-/-) mice compared with WT. Essentially IgG1 and IgG2c levels were detectable only in WT mice. C57-CD40L(-/-) animals, orally inoculated with 2 × 10(9) CFU, presented several clinical manifestations since the second week of infection and eventually died. In contrast at this time point no clinical manifestations were observed among C57-CD40L(-/-) mice infected with 1 × 10(7) CFU. Infection was subclinical in WT mice inoculated with either bacterial dose. The serum samples from infected mice (1 × 10(7) CFU), collected at day 14 after infection, had similar C. rodentium-specific IgM titres. Although C57-CD40L(-/-) animals had lower IgG and IgG2b titres than WT mice, C57-CD40L(-/-) mice sera displayed complement-mediated bactericidal activity against C. rodentium. C. rodentium-infected C57-CD40L(-/-) mice are capable of producing antibodies that are protective. C57-CD40L(-/-) mouse is a useful surrogate model of X-HIGM syndrome for studying immune responses elicited against pathogens.
authors.affiliation: Department of Molecular Biomedicine, CINVESTAV-IPN, Avenue IPN 2508, Zacatenco, 07360 México, DF, Mexico ; Department of Immunology, Escuela Nacional de Ciencias Biológicas IPN, Prolongación de Carpio y Plan de Ayala, 11340 México, DF, Mexico.
authors.forename: Catalina
authors.initials: C
authors.lastname: Lopez-Saucedo
authors.affiliation: Department of Molecular Biomedicine, CINVESTAV-IPN, Avenue IPN 2508, Zacatenco, 07360 México, DF, Mexico.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Bernal-Reynaga
authors.affiliation: Department of Molecular Biomedicine, CINVESTAV-IPN, Avenue IPN 2508, Zacatenco, 07360 México, DF, Mexico.
authors.forename: Jesus
authors.initials: J
authors.lastname: Zayas-Jahuey
authors.affiliation: Department of Infectomics and Molecular Pathogenesis, CINVESTAV-IPN, Avenue IPN 2508, Zacatenco, 07360 México, DF, Mexico.
authors.forename: Silvia
authors.initials: S
authors.lastname: Galindo-Gomez
authors.affiliation: Department of Infectomics and Molecular Pathogenesis, CINVESTAV-IPN, Avenue IPN 2508, Zacatenco, 07360 México, DF, Mexico.
authors.forename: Mineko
authors.initials: M
authors.lastname: Shibayama
authors.affiliation: Department of Immunology, Escuela Nacional de Ciencias Biológicas IPN, Prolongación de Carpio y Plan de Ayala, 11340 México, DF, Mexico.
authors.forename: Carlos
authors.initials: C
authors.lastname: Garcia-Galvez
authors.affiliation: Department of Immunology, Escuela Nacional de Ciencias Biológicas IPN, Prolongación de Carpio y Plan de Ayala, 11340 México, DF, Mexico.
authors.forename: Sergio
authors.initials: S
authors.lastname: Estrada-Parra
authors.affiliation: Department of Molecular Biomedicine, CINVESTAV-IPN, Avenue IPN 2508, Zacatenco, 07360 México, DF, Mexico.
authors.forename: Teresa
authors.initials: T
authors.lastname: Estrada-Garcia
mesh_terms: D000818:Animals; D019013:CD40 Antigens / Q000096:biosynthesis* / Q000276:immunology; D044082:Citrobacter rodentium / Q000472:pathogenicity; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D053307:Hyper-IgM Immunodeficiency Syndrome, Type 1 / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D056724:Immunity, Humoral / Q000235:genetics*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology*; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout
chemical_list: D019013:CD40 Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008024:Ligands