Investigating the immune response to central nervous system invasion by Brucella
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[EMBARGOED UNTIL 05/01/2026] Brucellosis is a zoonotic bacterial disease impacting millions of humans and domestic animals around the world. Responsible for billions of dollars in agricultural losses annually, the disease causes late term abortion in cattle, sheep, and goats, while mainly inducing flu-like symptoms and arthritis in humans. Modern antibiotics have helped to combat the acute phase of this debilitating illness however a large portion of patients experience lifelong effects due to the pathogen's persistence within the body. Despite being the most morbid complication of this disease, few research studies have evaluated neurobrucellosis in a laboratory setting and in turn, its pathogenesis is poorly understood. Here, we describe the first animal models of neurobrucellosis and uncover the pivotal role that innate lymphoid cells play in the prevention of disease. By utilizing various immunohistochemical stains, we became the first researchers to successfully visualize Brucella in the brains of experimentally-infected mice and suggested a potential method of entry within phagocytes. Additionally, adoptive transfers from both wild-type and IFN-g-deficient mice revealed that T cell mediated immunity is sufficient in both preventing and resolving established CNS infection in a neurobrucellosis mouse model in an IFN-g-dependent manner. Further analysis of this cytokine revealed that signaling through its receptors, IFN-a receptors, STAT1, and STAT2 all play crucial, interconnected protective roles in the development of disease. Our findings described here reveal numerous previously unknown characteristics of the immune response to CNS invasion by Brucella that have helped advance the understanding of this fatal complication and will hopefully improve treatment strategies and prevention of neurobrucellosis globally.
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Ph. D.