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

• Published in: BioMed research international 2015-01, Vol.2015 (2015), p.1-11
• Main Authors: Estrada-Garcia, Teresa, Garcia-Galvez, Carlos, Shibayama, Mineko, Galindo-Gomez, Silvia, Zayas-Jahuey, Jesus, Bernal-Reynaga, Rodolfo, Lopez-Saucedo, Catalina, Estrada-Parra, Sergio
• Format: Article
• Language: English
• Subjects: Animals; Antigens; Bacteria; Bacterial infections; CD40 Antigens - biosynthesis; CD40 Antigens - immunology; Citrobacter rodentium; Citrobacter rodentium - pathogenicity; Defects; Diarrhea; Disease Models, Animal; E coli; Gene Expression Regulation; Health aspects; Host-parasite relationships; Humans; Hyper-IgM Immunodeficiency Syndrome, Type 1 - genetics; Hyper-IgM Immunodeficiency Syndrome, Type 1 - immunology; Hyper-IgM Immunodeficiency Syndrome, Type 1 - pathology; Immunity, Humoral - genetics; Immunoglobulin G - blood; Immunoglobulin G - immunology; Immunoglobulin M - blood; Immunoglobulin M - immunology; Immunologic diseases; Infections; Ligands; Ligands (Biochemistry); Mice; Mice, Knockout; Observations; Patients; Physiological aspects; Rodents
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2015/679850

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 2×109 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 1×107 CFU. Infection was subclinical in WT mice inoculated with either bacterial dose. The serum samples from infected mice (1×107 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.