Dietary whey protein increases brain leukocytes in mice regardless of their hypersensitivity status

Abstract

Abstract Cow’s milk allergy (CMA) often manifests as milder reactions and may be linked to neurological problems. Previously, we demonstrated that C57BL/6J mice sensitized to a bovine whey allergen, β-lactoglobulin (BLG, Bos d 5), moderately increased BLG-specific IgE levels and exhibited behavioral changes without severe allergic reactions. When these non-anaphylactic CMA mice were placed on a whey-protein (WP)-containing diet for 2 weeks to simulate continuous dairy consumption, we found neuropathology indicative of neuroinflammation and cortical demyelination. Since immune cells migrate to the central nervous system (CNS) and promote neuroinflammation in demyelinating conditions such as multiple sclerosis, we hypothesized that the number of leukocytes would increase in BLG-sensitized mouse brains to orchestrate neuropathology. To test this hypothesis, we used flow cytometry to determine the number and phenotypes of leukocytes in the brains of naïve, sham, and BLG-sensitized mice after the 2 weeks of the WP diet. The frequencies of cells expressing common leukocyte marker CD45, pan T cell marker CD3, cytotoxic T cell marker CD8, integrin CD11b, myeloid cell marker CD14, and co-stimulatory marker CD86 significantly increased, regardless of the sensitization status. The percentages of these cells were low in mice that never received WP. This result indicated that WP diet consumption alone increased CNS leukocyte populations. Additional immunophenotyping is needed to determine whether the identified cells can be differentiated among the experimental groups. Detailed characterization of CNS leukocyte phenotypes and dynamics will help elucidate the mechanism of CMA-induced neuroinflammation and cortical demyelination.