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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.
- Source :
-
BioMed research international [Biomed Res Int] 2015; Vol. 2015, pp. 679850. Date of Electronic Publication: 2015 May 03. - Publication Year :
- 2015
-
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.
- Subjects :
- Animals
CD40 Antigens immunology
Citrobacter rodentium pathogenicity
Disease Models, Animal
Gene Expression Regulation
Humans
Hyper-IgM Immunodeficiency Syndrome, Type 1 genetics
Hyper-IgM Immunodeficiency Syndrome, Type 1 pathology
Immunoglobulin G blood
Immunoglobulin G immunology
Immunoglobulin M blood
Ligands
Mice
Mice, Knockout
CD40 Antigens biosynthesis
Hyper-IgM Immunodeficiency Syndrome, Type 1 immunology
Immunity, Humoral genetics
Immunoglobulin M immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2314-6141
- Volume :
- 2015
- Database :
- MEDLINE
- Journal :
- BioMed research international
- Publication Type :
- Academic Journal
- Accession number :
- 26064940
- Full Text :
- https://doi.org/10.1155/2015/679850