Dietary allergen promotes sex-specific leukocyte trafficking and alters the brain immune cell populations in subclinically sensitized mice.

Abstract

Dietary allergens can affect mood and cognition in some sensitized individuals without eliciting immediate or severe physical reactions. However, if these "subclinically sensitized," allergen-tolerant individuals continue to consume offending allergens, they may be at a greater risk of chronic peripheral inflammation that affects brain function and behavior via neuroinflammation. To elucidate potential mechanisms by which immune responses to consumed allergens are communicated to the central nervous system (CNS), we investigated the accumulation of leukocytes in the brain and the trafficking of peripheral leukocytes to the CNS in our mouse model of subclinical cow's milk allergy (CMA). Male and female C57BL/6J mice were sensitized to a bovine β-lactoglobulin (BLG, Bos d 5) or the vehicle alone and subsequently placed on an allergen-containing diet for 2 weeks. The activity and cognitive function of the mice were assessed by a series of behavioral tests, and the number and phenotypes of the leukocytes in the brain were determined by flow cytometry and immunofluorescence. The frequencies of CXCR5⁺ leukocytes were significantly elevated, specifically in BLG-sensitized male mice after allergen consumption. Immunostaining showed that the increases in CXCR5⁺ cells were most evident in the dorsomedial frontoparietal cortical regions, where CMA-associated microgliosis was observed. However, the majority of these cells were neurons, and CXCR5⁺ peripheral leukocytes primarily accumulated in the rostral-rhinal hub region of the dura mater. These results suggest that allergen consumption by subclinically sensitized individuals prompts CXCR5-mediated leukocyte chemotaxis to the dura and alters cortical neuron phenotype, presenting a potential mechanism for peripherally triggered neuroinflammation.