Cryptococcus neoformans meningitis in the rat

David L. Goldman, Arturo Casadevall, Youngsoo Cho, Sunhee C. Lee

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The primary clinical manifestation of Cryptococcus neoformans infection in humans is meningoencephalitis. To study the defense mechanisms that participate in the host response against C. neoformans infection of the central nervous system (CNS), we have developed a new model of cryptococcal meningitis in rats. Intracisternal inoculation of C. neoformans produced a granulomatous meningitis with minimal brain parenchymal involvement, resembling cryptococcal meningitis in immunocompetent patients. The granulomas were composed of T cells (CD4+ and CD8+) and macrophages (CD11b/c+); a subpopulation of the macrophages expressed inducible nitric oxide synthase (NOS2). In this model, C. neoformans disseminated to systemic organs early in the course of infection and provoked granuloma formation and NOS2 expression. The temporal profile of inflammation indicated that the CNS inflammatory response is delayed relative to that in the lung and the spleen, which suggests that the effective inflammatory response within the CNS may follow activation of T cells in the periphery and their subsequent entry into the CNS. Inflammation in the meninges was associated with signs of subpial and subependymal glial activation, including enhanced expression of CD11b/c and CD4 in microglia and glial fibrillary acidic protein in astrocytes. Neither cells, however, expressed NOS2. Although C. neoformans invasion to the brain parenchyma was rare, soluble polysaccharide was commonly associated with reactive glial cells. Necrosis was not a feature of C. neoformans granulomas, but, instead, inflammatory cells underwent apoptosis in inflamed organs. The current rat intrathecal cryptococcosis model has several unique advantages for the study of human cryptococcal meningoencephalitis that include close resemblance of histopathologic changes to those in humans, easy accessibility to the cerebrospinal fluid compartment, and no requirement of immunosuppressive agents for establishment of infection.

Original languageEnglish (US)
Pages (from-to)759-770
Number of pages12
JournalLaboratory Investigation
Volume75
Issue number6
StatePublished - Dec 1996

Fingerprint

Cryptococcus neoformans
Meningitis
Granuloma
Cryptococcal Meningitis
Meningoencephalitis
Central Nervous System
Neuroglia
Infection
Macrophages
Inflammation
T-Lymphocytes
Central Nervous System Infections
Meninges
Cryptococcosis
Glial Fibrillary Acidic Protein
Brain
Microglia
Nitric Oxide Synthase Type II
Immunosuppressive Agents
Astrocytes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Goldman, D. L., Casadevall, A., Cho, Y., & Lee, S. C. (1996). Cryptococcus neoformans meningitis in the rat. Laboratory Investigation, 75(6), 759-770.

Cryptococcus neoformans meningitis in the rat. / Goldman, David L.; Casadevall, Arturo; Cho, Youngsoo; Lee, Sunhee C.

In: Laboratory Investigation, Vol. 75, No. 6, 12.1996, p. 759-770.

Research output: Contribution to journalArticle

Goldman, DL, Casadevall, A, Cho, Y & Lee, SC 1996, 'Cryptococcus neoformans meningitis in the rat', Laboratory Investigation, vol. 75, no. 6, pp. 759-770.
Goldman DL, Casadevall A, Cho Y, Lee SC. Cryptococcus neoformans meningitis in the rat. Laboratory Investigation. 1996 Dec;75(6):759-770.
Goldman, David L. ; Casadevall, Arturo ; Cho, Youngsoo ; Lee, Sunhee C. / Cryptococcus neoformans meningitis in the rat. In: Laboratory Investigation. 1996 ; Vol. 75, No. 6. pp. 759-770.
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