UC Davis

During respiratory tract viral infections, a coordinated immune response is initiated, with innate immune cells detecting the virus and mounting an immediate, crucial protective response. Subsequently, the adaptive immune system, involving B and T cells, generates protective antibodies, eliminates remaining infected cells, and establishes immune memoryfor future protection. There are times, however, when the immune system orchestration is disrupted and dysregulated, resulting in self-damage and diminishing host survival. Dysregulated innate inflammatory pathways, characterized by excessive cytokine production (known as a “cytokine storm”), can exacerbate respiratory pathology and systemic inflammation, highlighting the necessity for balanced immune activation. Despite advancements in understanding these pathways, identifying control mechanisms for pulmonary inflammation, particularly in respiratory viral infections, remains critical as poor outcomes are associated with uncontrolled inflammation. Other times, induction of a poor adaptive immune response may offer little to no protection against infections. Within the adaptive immune system, B cells contribute to protection through two distinct reactions: an early protective extrafollicular response (EFR) and the germinal center (GC) response. While the latter is extensively studied and well understood, the preceding, protective EFR, along with the signals that promote it, require further investigation. Over the past decades, there has been growing evidence of nervous and immune systems co-evolution, with both systems expressing common receptors and signals. Thus, it is reasonable to hypothesize that these two systems may interact. Acetylcholine (ACh), produced through the action of choline acetyltransferase (ChAT), is a major neurotransmitter, facilitating signaling between pre- and post-synaptic neurons, as well as between nerve cells and muscle or gland cells. Although primarily associated with neurons and the regulation of parasympathetic autonomic functions and muscle contractions, recent research has revealed a role for ACh in the interplay between nervous and immune systems and ACh-producing lymphocytes as modulators of immunity. Deciphering the intricate signals orchestrating this immune dance ignites a spark of curiosity in the minds of immunologists. This dissertation aims to explore how ACh derived from B and T cells, along with ACh receptors, regulate innate and adaptive immunity. Understanding these mechanisms could provide insights into therapeutic targets for controlling immune responses and improving outcomes. following respiratory viral infections.