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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
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Apoptosis induction by glucuronoxylomannan of Cryptococcus neoformans

L S Chiapello1, M P Aoki, H R Rubinstein

  • 1Micología, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.

Medical Mycology
|September 11, 2003
PubMed

Insights

Glucuronoxylomannan (GXM) from Cryptococcus neoformans induces apoptosis, or programmed cell death, in rat lymphocytes. This GXM-induced apoptosis may contribute to the immunosuppression seen in cryptococcosis infections.

Area of Science:

  • Immunology
  • Cell Biology
  • Microbiology

Background:

  • Cryptococcus neoformans is a fungal pathogen causing cryptococcosis.
  • Glucuronoxylomannan (GXM) is the primary component of the C. neoformans capsule.
  • The immunosuppressive mechanisms of cryptococcosis are not fully understood.

Purpose of the Study:

  • To investigate the in vitro and in vivo effects of GXM on lymphocyte apoptosis.
  • To determine if GXM contributes to the immunosuppression observed during C. neoformans infection.

Main Methods:

  • Spleen mononuclear cells (Smc) from normal rats were treated with GXM.
  • DNA content and fragmentation were analyzed using propidium iodide staining and gel electrophoresis.
  • Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) assay was used to detect apoptotic cells.
  • Apoptosis was also assessed in lung and spleen tissues from rats infected with C. neoformans.

Main Results:

  • GXM treatment increased hypodiploidy and DNA fragmentation in rat Smc.
  • GXM-treated T-cell receptor (TCR+) cells showed increased hypodiploidy.
  • TUNEL labeling revealed a high number of apoptotic cells in GXM-treated Smc.
  • Infected rats exhibited significant apoptosis in lung and spleen tissues.

Conclusions:

  • GXM induces apoptosis in lymphocytes in vitro.
  • GXM-induced apoptosis is a potential mechanism of immunosuppression in C. neoformans infection.
  • Programmed cell death mediated by GXM may play a role in the pathogenesis of cryptococcosis.

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