Master of Science (MS), Wright State University, 2017, Physiology and Neuroscience

The carotid bodies (CB), the primary peripheral chemoreceptors, respond to changes in blood gases with neurotransmitter release, thereby increasing carotid sinus nerve firing frequency and ultimately correcting the pattern of breathing. It has previously been demonstrated that acute application of the adipokine leptin caused perturbations of intracellular calcium and membrane ion movement in isolated CB Type I cells (Pye et al, 2015) and augmented the response of the intact CB to hypoxia (Pye et al, 2016). This study's aim was to examine, in-vivo, if elevated leptin modulated CB function and breathing. Rats were fed high-fat chow or control chow for 16-weeks. High-fat fed (HFF) animals gained significantly more weight compared to control fed (CF) animals (n=18; p<.001; 512.56 g ± 14.70 g vs. 444.11 g ± 7.09 g). HFF animals also had significantly higher serum leptin levels compared to CF (n=18; p<.0001; 3.05 ng/mL ± 0.24 ng/mL vs. 1.29 ng/mL ± 0.12 ng/mL). Whole-body plethysmography was used to test the acute hypoxic ventilatory response (HVR) in unrestrained, conscious animals. HFF animals had an attenuated 2nd-phase of the HVR when compared to CF (n=18; p<.05; 710.1 ± 41.9 mL kg-1 min-1 vs. 855.4 ± 44.05 mL kg-1 min-1). CB Type I cells were isolated and intracellular calcium measured; no significant differences in the cellular hypoxic responses between groups were observed. These data show differences in the 2nd-phase of the HVR caused by high fat feeding are unlikely to be caused by an action of leptin on the Type I cells. However the possibility remains that leptin may have in-vivo postsynaptic effects on the carotid sinus nerve; this remains to be investigated.

Committee: Christopher Wyatt Ph.D. (Advisor); Eric Bennett Ph.D. (Other); David Ladle Ph.D. (Committee Member); Mark Rich M.D./Ph.D. (Committee Member); Robert Fyffe Ph.D. (Other) Subjects: Biology; Cellular Biology; Neurosciences; Physiology

Master of Science, The Ohio State University, 2024, Immunology and Microbial Pathogenesis

Bordetella bronchiseptica is a respiratory pathogen with a broad host range, primarily infecting dogs, cats, pigs, and rabbits. It is one of the causative agents of canine infectious respiratory disease complex (CIRDC), or “kennel cough”. CIRDC poses a significant threat due to its highly contagious nature, leading to frequent outbreaks in canine populations. In addition, interspecies transmission and zoonotic transmission to immunocompromised humans has been reported. There are three different types of vaccines used to protect against this pathogen: live attenuated, whole cell, and cellular antigen extract vaccines. Of these three vaccines, intranasal and oral live attenuated B. bronchiseptica is commonly used to prevent infections in dogs. Despite widespread use, our understanding of the mucosal immune response elicited by these vaccines is limited. In addition, these vaccines do not fully protect against transmission of B. bronchiseptica, and dogs require a booster every 6 to 12 months. Therefore, there is a need for novel vaccine formulations to reduce bacterial burden and disease severity of B. bronchiseptica. We developed a subunit vaccine containing B. bronchiseptica antigens FHA, Prn, and BcfA, a dual antigen-adjuvant. BcfA has been shown to be a protective antigen following intramuscular immunization and capable of polarizing a Th1/Th17 immune response in mice. We utilized a “prime-pull” and intranasal prime-boost immunization strategy to elicit enhanced mucosal immunity. To understand vaccine-driven immunity, we measured the production of cytokines by tissue-resident CD4+ T prior to infection and the recruitment of phagocytes to mucosal tissue after infection. In addition, we enumerated CFUs at multiple days post infection in the lungs and nasal tissue. We used whole-body plethysmography to noninvasively measure respiratory impairment to evaluate protection by vaccination. Both immunization strategies elicited a Th1/Th17 phenotype and antibody response (open full item for complete abstract)

Committee: Purnima Dubey PhD (Advisor); Kara Corps DVM, PhD (Committee Member); Jacob Yount PhD (Committee Member) Subjects: Biomedical Research; Immunology