Browsing by Author "Fusco, Elizabeth Michelle"

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    Characterizing the Formation and Functionality of Immune Memory Cells in Response to Plasmodium Infection
    (2025-05) Fusco, Elizabeth Michelle; Schmidt, Nathan W.; Absalon, Sabrina; Bauer, Margaret; Longtin, Krista; Luo, Wei; Richer, Martin
    Malaria is an infectious disease caused by Plasmodium parasites. Over 40% of the world lives in malaria endemic regions, and children under the age of 5 in Sub-Saharan Africa face the highest burden of this disease. The clinical symptoms of malaria are caused by the cyclical infection and rupture of red blood cells by Plasmodium, and these parasites are cleared from the blood by the immune system. Plasmodium infection does not induce sterilizing immunity; however, individuals can generate clinical immunity to malaria after repeated exposures, but the factors that regulate this process are poorly understood. An emerging modulator of the immune response is the gut microbiome. We previously identified that the composition of the gut microbiome correlates with the outcome of Plasmodium infections in African children and impacts ability of the immune system to fight a Plasmodium infection in mice. We next investigated how the gut microbiome impacts the immune memory response in mice. We determined that the gut microbiome influences the formation of memory B cells and memory T cells during primary Plasmodium yoelii infection. Furthermore, the gut microbiome governs the ability of these immune memory cells to mount a secondary germinal center (GC) response to a Plasmodium berghei ANKA challenge. Curiously, the gut microbiome did not affect the accumulation of plasma cells (PCs) in the bone marrow following P. yoelii infection, and we observed that antigen-specific PC accumulation was poor. It is hypothesized that PCs are important for protection against reinfection with Plasmodium due to their ability to secrete high-affinity antibodies. We next characterized how P. yoelii infection impacted the generation and maintenance of PCs. We discovered that P. yoelii infection impairs the ability of the GC to produce long-lived PCs (LLPCs). Additionally, P. yoelii alters the composition of the bone marrow, negatively impacting the ability of PCs to engraft in the bone marrow as LLPCs. These defects in the generation and maintenance of P. yoelii-induced LLPCs likely impairs the ability of the immune system to protect against future Plasmodium infections.