Cryptococcus neoformans capsular glucuronoxylomannan induces expression of Fas ligand in macrophages

Claudia Monari, Eva Pericolini, Giovanni Bistoni, Arturo Casadevall, Thomas R. Kozel, Anna Vecchiarelli

Research output: Contribution to journalArticle

Abstract

The major component of capsular material of Cryptococcus neoformans is glucuronoxylomannnan (GXM), a polysaccharide that exhibits potent immunosuppressive properties in vitro and in vivo. The results reported here show that 1) soluble purified GXM induces a prompt, long-lasting, and potent up-regulation of Fas ligand (FasL) on macrophages, 2) the up-regulation of FasL is related to induced synthesis and increased mobilization to the cellular surface, 3) this effect is largely mediated by interaction between GXM and TLR4, 4) FasL up-regulation occurs exclusively in GXM-loaded macrophages, 5) macrophages that show up-regulation of FasL induce apoptosis of activated T cells expressing Fas and Jurkat cells that constitutively express Fas, and 6) anti-Fas Abs rescue T cells from apoptosis induced by GXM. Collectively our results reveal novel aspects of the immunoregulatory properties of GXM and suggest that this nontoxic soluble compound could be used to dampen the immune response, to promote or accelerate the death receptor, and to fix FasL expression in a TLR/ligand-dependent manner. In the present study, we delineate potential new therapeutic applications for GXM that exploit death receptors as key molecular targets in regulating cell-mediated cytotoxicity, immune homeostasis, and the immunopathology of diseases.

Original languageEnglish (US)
Pages (from-to)3461-3468
Number of pages8
JournalJournal of Immunology
Volume174
Issue number6
DOIs
StatePublished - Mar 15 2005

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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