Moreira, T. G. | bioRxiv Science

bioRxiv2026

Intranasal Anti-CD3 Antibody Treatment Attenuates Post-COVID Neuroinflammation and Enhances Hippocampal Neurogenesis and Cognitive Function in Mice

Cognitive impairment is a disabling feature of Long COVID, with data supporting neuroinflammation and maladaptive glial responses as primary drivers. Nasal administration of an anti-CD3 monoclonal antibody (aCD3 mAb) has shown therapeutic benefits in autoimmune and CNS disease models. Using a respiratory-restricted mild SARS-CoV-2 mouse model of Long COVID, we show that nasal anti-CD3 mAb, administered shortly after infection or during chronic neuroinflammation, increased brain FoxP3+ IL-10+ Tregs, reduced microglial and astrocytic gliosis in the white matter and hippocampus, restored neurogenesis, and improved short-term memory. Nasal aCD3 mAb reprogrammed microglia from an antigen-presenting, NF-{kappa}B-driven inflammatory state toward chemokine signaling, phagosome, and TGF {beta}-related regulatory phenotype. Patients with Long COVID with neurological symptoms had lower circulating Treg populations. These findings identify nasal administration of aCD3 mAb as a noninvasive strategy to control neuroinflammation, restore the neurogenic niche, and offer a novel approach to treating cognitive impairment in Long COVID.

immunology↗

bioRxiv2020

Neuroimmune circuits involved in β-lactoglobulin-induced food allergy

Cows milk allergy is the most prevalent food allergy that usually begins early in life and {beta}- lactoglobulin (BLG) is the milk component with the highest allergenicity. It has been described that ovalbumin (OVA)-induced food allergy in mice is associated with anxiety and aversive behavior. However, it is yet to be determined whether altered behavior is a general component of food allergy or whether it is specific for some types of allergens. Thus, we investigated behavioral and neuroimmune circuits triggered by allergic sensitization to BLG. We found a neuroimmune conflict between aversion and reward in a model of food allergy induced to BLG. Mice sensitized to BLG did not present aversive behavior when the allergen was used for sensitization and oral challenge. Mice allergic to BLG preferred to drink the allergen-containing solution over water even though they presented high levels of specific IgE, inflammatory cells in the intestinal mucosa and significant weight loss. When sensitized to OVA and orally challenged with the same antigen, mice had display neuron activation in the amygdala suggesting an anxiety-related sensation. On the other hand, OVA-sensitized mice showed preference to consume a mixture of BLG and OVA during oral challenge in spite of their aversion to OVA. Consumption of OVA-BLG solution was associated with neuron activation in the nucleus accumbens, suggesting a reward sensation. Thus, the aversive behavior observed in food allergy to OVA does not apply to all antigens and some allergens may induce preference rather than aversion. Our study provides new insights into the neuroimmune conflicts regarding preference and avoidance to a common antigen associated with food allergy.

immunology↗