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Binding and Internalization of Glucuronoxylomannan, the Major Capsular Polysaccharide of Cryptococcus neoformans, by Murine Peritoneal Macrophages
AdvisorKozel, Thomas R.
Biochemistry and Molecular Biology
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Cryptococcus neoformans (C. neoformans) infection is of particular importance in modern medicine. C. neoformans is an encapsulated fungus which largely causes opportunistic infections, especially in AIDS or other immunocompromised patients. Due to a strong tropism for the central neural system, C. neoformans is the most common cause of fungal meningoencephalitis. Prior to the implementation of HAART (highly active antiretroviral therapy), up to 5-10% of US patients with AIDS developed cryptococcosis. In humans, the encapsulated yeast C. neoformans is transmitted by inhalation into the alveolar spaces and causes severe life-threatening pneumonia, meningitis, as well as disease in other organ diseases (cryptococcosis). Furthermore, cryptococcosis is a worldwide disease. The polysaccharide capsule of C. neoformans, the major virulence factor, is composed chiefly of glucuronoxylomannan (GXM) and two minor constituents, galactoxylomannan (GalXM) and mannoprotein (MP). The capsule's interactions with the systems of innate and adaptive immunity modulate the host immune reaction against C. neoformans infection. With the emerging importance of protective immune responses mediated by innate and adaptive immunity, the regulation and molecular mechanisms during C. neoformans infection or pathogenesis have begun to unfold. The two main foci of attention in this study of C. neoformans are as follows:(1) Host immune reactions against C. neoformans infection (Chapter 1)(2) Binding and internalization of glucuronoxylomannan (GXM), the major capsular polysaccharide of C. neoformans, by murine peritoneal macrophages (Chapter 2) Chapter 1 provides an overview of the nature of GXM or C. neoformans and recent advances regarding the interaction of the host immune system with GXM or C. neoformans that include the Th1-dominated response and complement- and antibody-mediated rapid anti-GXM capsular host defense reactions. Chapter 2 describes the central research aim, which is to examine selected cellular mechanisms for binding and uptake of GXM by murine peritoneal macrophages. I hope that the information from Chapter 1 and Chapter 2 may contribute to an understanding of how to facilitate the host response against C. neoformans infection and yield new insights into future immunomodulatory strategies for the treatment of C. neoformans infection.