Project: Research project

Project Details


C. neoformans causes a life-threatening meningoencephalitis in about 10%
of patients with AIDS. The pathogenesis of cryptococcal infections is
poorly understood. We propose to answer basic questions of C. neoformans
pathogenesis using a rat model system. Over the past year Dr. Goldman has
developed various rat models of cryptococcosis and these offfer
significant advantages over existing animal systems. The time course of
infection will be studied by characterizing the cellular, cytokine, and
antibody responses. Cryptococcal meningoencephalitis will be established
by infusion of C. neoformans into the rat cerebrospinal bluid. The host
response in the brain will be studied including tghe cellular response and
cytokine induction profile in the brain. A model of reactivation with
immunosuppression will be developed to explore the pathogenesis of
reactivation disease. Monoclonal antibodies (mAbs) to C. neoformans
polysaccharide will be generated from rats. Rat mAbs will be characterizd
serologically, molecularly, and by competition with pre-existing mouse
mAbs. The rat mAbs will be used to study the pharmacokinetics of C.
neoformans capsular glucuronoxylomannan (GXM) in the presence and absence
of antibody. Although GXM is an established immunomodulator which
accumulates in body tissues and contributes to virulence, relatively
little is known about the fate of GXM in infection. The organ
distribution and half-life of GXM will be studied using ELISA and
radiolabelled antibody and GXM derivatives. mAbs will also be used to
explore passive antibody protection in the rat and the potential of
antibody to be used for imaging. Preliminary data indicates that
radiolabelled antibody to GXM can be used to image an infection.
Radiolabelled imaging offers a powerful tool for studying the pathogenesis
of infection.
Effective start/end date8/1/957/31/00


  • Immunology


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