Comparison of cow's milk allergy models highlighted higher humoral and Th2 immune responses in BALB/c than C3H/HeNCrl mice

Abstract

Cow's milk allergy (CMA) is common in early childhood and the incidence is increasing. However, its mechanisms of action are still not fully understood due to the range of different clinical symptoms. So far, the development of different mouse models has been the best choice to study the molecular mechanisms triggering allergy. However, the selection of suitable strains for the establishment of animal models truly representative of associated human pathologies is still a challenge. Hence, we focused on both C3H/HeNCrl and BALB/c mice to characterize their susceptibility to CMA. After intraperitoneal sensitization, BALB/c and C3H/HeNCrl strains were challenged with β-lactoglobulin (BLG), and compared in allergic symptoms and active immune response, which assessed by specific antibody production and cytokine release. At first, both groups exhibited anaphylaxis, showed specific BLG-related IgE, Th2 response and seemed both suitable for the development of CMA models. However, a detailed analysis revealed that BALB/c had both stronger humoral and Th2 immune responses, producing more antibodies (IgE and IgG/IgG1/IgG2a), and releasing higher levels of Th2-associated cytokines (IL-4, IL-5, IL-13) compared to C3H/HeNCrl mice. Therefore, BALB/c strain would represent a preferential choice in the establishment of CMA models. This study highlights the subtle differences and major outcomes in the selection of mouse strains for the development of suitable food allergy models.