Nociceptor Neurons Control Vaccine-Induced Immunity
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Authors
Gupta, Surbhi
Date
2025-08-18
Type
thesis
Language
eng
Keyword
sensory neurons , dorsal root ganglia , nociceptors , calcitonin gene-related peptide , vaccines , influenza A virus , immune response , T cells , dendritic cells , IgG
Alternative Title
Abstract
Nociceptors, the sensory neurons that detect noxious stimuli and trigger pain, actively regulate immune responses. They directly innervate lymph nodes and the spleen, where they influence lymphatic endothelial cells and germinal center B cells via neuropeptides such as calcitonin gene-related peptide (CGRP), shaping antibody production, germinal center dynamics, and both innate and adaptive immunity during bacterial and viral infections. In this thesis, I investigated whether nociceptors respond to vaccine adjuvants and modulate vaccine-induced immunity and antiviral defense. Using calcium microscopy, I activated and sensitized mouse sensory neurons with vaccines and adjuvants against influenza virus and pneumococcal and meningococcal bacteria in vitro, evaluated influenza vaccine-specific IgG antibody levels by ELISA, and characterized immune responses in vaccinated mice post-infection using flow cytometry. Our results showed that sensory neurons respond to vaccines, exhibit differential activation across noxious ligands, and release CGRP. Using both genetic and chemical models of nociceptor ablation, I found that nociceptor loss did not impair vaccine-specific IgG production but selectively altered cellular immune responses, particularly T cell, inflammatory monocyte, macrophage, and dendritic cell activation and localization, suggesting a selective regulatory role for nociceptors in coordinating innate-adaptive immune crosstalk, likely by influencing antigen presentation and immune priming. Together, this work supports an emerging paradigm in which nociceptive neurons are not passive but function as integral modulators of vaccine-induced immunity and antiviral defense. These findings have broad implications for the design of next- generation vaccines that synergize immune and neural components to optimize protective immunity while potentially reducing vaccine reactogenicity.
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Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
Attribution-NonCommercial-NoDerivatives 4.0 International