Involvement of glycoreceptors in galactoxylomannan-induced T cell death

Eva Pericolini, Elena Gabrielli, Elio Cenci, Magdia De Jesus, Francesco Bistoni, Arturo Casadevall, Anna Vecchiarelli

Research output: Contribution to journalArticle

Abstract

The major virulence factor of Cryptococcus neoformans is its capsular polysaccharide, which is also released into tissues. The shed polysaccharide is composed of glucuronoxylomannan, galactoxylomannan (GalXM), and mannoproteins. In a previous study, we demonstrated a direct interaction of purified soluble GalXM with T cells that induced their apoptosis. In this study, we focus on the mechanisms involved in the apoptotic effect of GalXM. In our experimental system, we analyzed the effect of GalXM on purified human T cells and Jurkat cells, a T cell line routinely used for apoptotic studies. Our results reveal that GalXM activates the extrinsic and intrinsic apoptotic pathways through the cleavage and recruitment of caspase-8. Caspase-8 elicits the downstream executioner caspase-3, caspase-6, and caspase-7 both directly and indirectly, via Bid cleavage and caspase-9 activation. These effects appeared to be primarily mediated by the interaction of GalXM with the glycoreceptors, which differed in human T and Jurkat cells. CD45 was primarily involved in Jurkat cells apoptosis while CD7 and CD43 mediated human T cell apoptosis. Our results highlight a new mechanism by which a microbial product can contribute to virulence through direct interaction with T cell glycoreceptors, thereby triggering lymphocyte apoptosis.

Original languageEnglish (US)
Pages (from-to)6003-6010
Number of pages8
JournalJournal of Immunology
Volume182
Issue number10
DOIs
StatePublished - May 15 2009
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Pericolini, E., Gabrielli, E., Cenci, E., De Jesus, M., Bistoni, F., Casadevall, A., & Vecchiarelli, A. (2009). Involvement of glycoreceptors in galactoxylomannan-induced T cell death. Journal of Immunology, 182(10), 6003-6010. https://doi.org/10.4049/jimmunol.0803833