MICaB Graduate Program
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Kirsten Nielsen, Ph.D
Department of Microbiology and Immunology
North Carolina State University, 2001, Ph.D.
office - 612-625-4979
lab - 612-625-4975
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.
Selected Recent Publications:
- Gerstein, AC, Fu, MS, Mukaremera, L, Li, Z, Ormerod, KL, Fraser, JA, Berman, J, and Nielsen, K. 2015. Polyploid titan cells produce haploid and aneuploidy progeny to promote stress adaptation. MBio, 6:e01340-15.
- Wiesner, DL, Smith, KD, Kotov, DI, Nielsen, JN, Bohjanen, PR, and Nielsen, K. 2015. Regulatory T cell induction and retention in the lung is necessary for suppression of detrimental type-2 helper T cells during pulmonary cryptococcal infection. Journal of Immunology, 196(1):365-74.
- Smith*, KD, Achan*, B, McDonald, T, Okagaki, L, Akampurira, A, Huppler-Hullsiek, K, Meya, DB, Boulware, DR, and Nielsen, K. 2015. Increased antigungal drug resistance in Ugandan clinical isolates of Cryptococcus neoformans. Antimicrobial Agents and Chemotherapy, 59:7197-204.
- Wiesner, DL, Specht, CA, Lee, KO, Smith, KD, Lee, CG, Mukaremera, L, Lee, ST, Lee, CG, Elias, JA, Nielsen, JN, Boulware, DR, Bohjanen, PR, Jenkins, MK, Levitz, SM, and Nielsen, K. 2015. Chitin recognition via chitotriosidase promotes pathologic type-2 helper T cell responses to cryptococcal infection. PLoS Pathogens, 11:e1004701.
- Wiesner*, DL, Moskalenko*, O, Corcoran, JM, McDonald, T, Rolfes, MA, Meya, DB, Kajumbula, H, Knight, JF, Boulware, DR, and Nielsen, K. 2012. Cryptococcal genotype influences immunologic response and human clinical outcome after meningitis. mBio, 3:e00196-12.
- Crabtree*, JH, Okagaki*, LH, Strain, AK, Nielsen, JN, and Nielsen, K. 2012. Titan cell production enhances virulence of Cryptococcus neoformans. Infection and Immunity, 80:3776-378.
- Okagaki, LH, and Nielsen, K. 2012. Titan cells confer protection from phagocytosis in Cryptococcus neoformans infections. Eukaryotic Cell, 11:820-826.
- Okagaki, LH, Wang, Y, Ballou, ER, O'Meara, TR, Bahn, YS, Alspaugh, JA, Xue, C, and Nielsen K. 2011. Cryptococcal titan cell formation is regulated by G-protein signaling in response to multiple stimuli. Eukaryotic Cell, 10:1306-16
- Okagaki*, LH, Strain*, AK, Charlier, C, Nielsen, JN, Baltes, NJ, Chretien, F, Heitman, J, Dromer, F, and Nielsen, K. 2010. Cryptococcal cell morphology affects host cell interactions and pathogenicity. PLoS Pathogens, 6:e10000953.