Capsular polysaccharide induction of apoptosis by intrinsic and extrinsic mechanisms

Claudia Monari1, Francesca Paganelli, Francesco Bistoni

  • 1Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.

Cellular Microbiology
|July 24, 2008
PubMed

Insights

Glucuronoxylomannan (GXM) from Cryptococcus neoformans triggers lymphocyte apoptosis by activating both extrinsic and intrinsic cell death pathways within a single cell. This mechanism offers potential for therapeutic applications in modulating T-cell responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Microbial Pathogenesis

Background:

  • Cryptococcus neoformans glucuronoxylomannan (GXM) induces lymphocyte apoptosis via Fas ligand (FasL) on macrophages.
  • Understanding the precise molecular mechanisms of GXM-induced apoptosis is crucial for exploring therapeutic interventions.

Purpose of the Study:

  • To elucidate the molecular pathways mediating GXM-induced lymphocyte apoptosis in vitro and in vivo.
  • To investigate the interplay between extrinsic and intrinsic apoptotic pathways in GXM-treated cells.

Main Methods:

  • Cytofluorimetric analysis to assess cellular events.
  • Western blotting to detect protein cleavage and activation.
  • Experimental model of murine candidiasis for in vivo validation.

Main Results:

  • GXM upregulates FasL on macrophages, leading to lymphocyte apoptosis.
  • Both caspase 8 (extrinsic) and caspase 9 (intrinsic) pathways are activated within the same cell, forming an amplification loop.
  • GXM-mediated caspase 8 activation and apoptosis were confirmed in a murine candidiasis model.

Conclusions:

  • GXM-induced apoptosis involves a coordinated cross-talk between extrinsic and intrinsic apoptotic pathways within a single cell.
  • This intricate apoptotic mechanism highlights GXM's potential for therapeutic use in controlling T-cell-mediated immune responses.

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