Central Nervous System Penetration by Cryptococcus neoformans Fungal infections affect billions of people every year, often causing lethal disease in immunocompromised individuals. Of particular concern are invasive fungal infections, estimated to kill one and a half million people annually. Cryptococcus neoformans infections cause almost half of all deaths due to fungal infection. Even with access to the best available antifungals, Cn mortality rates of 20-40% remain unacceptably high. Although natural immunity to fungal infection is quite efficient in immune replete humans, disease in immune deficient individuals is often a complex interaction between failure to control fungal replication and an inappropriate immune response. My research program focuses on understanding how Cryptococcus causes disease, with the goal of developing better treatment strategies that improve patient survival. Our research primarily focuses on studies to understand the novel "titan cell" morphology during Cryptococcus infection. Upon inhalation, Cryptococcus establishes an initial pulmonary infection that eventually disseminates to the central nervous system (CNS) to cause meningitis. In response to the host pulmonary environment, a subset of Cryptococcus cells become titan cells that are 5-10x larger than typical-sized cells. These titan cells are critical for virulence, impact dissemination to the CNS, and their production during the infection dramatically alters the host response by reducing phagocytosis and stimulating a detrimental Th2-mediated response. Our current research is aimed at understanding the molecular mechanisms and host-pathogen interactions underlying the activity of titan cells during infection.
