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

Catalina Lopez-Saucedo, Rodolfo Bernal-Reynaga, Jesus Zayas-Jahuey, Silvia Galindo-Gomez, Mineko Shibayama, Carlos Garcia-Galvez, Sergio Estrada-Parra, Teresa Estrada-Garcia

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Abstract

Copyright © 2015 Catalina Lopez-Saucedo et al. 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.
Original languageAmerican English
JournalBioMed Research International
DOIs
StatePublished - 1 Jan 2015

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