Involvement of glycoreceptors in galactoxylomannan-induced T cell death.
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.
Department of Experimental Medicine and Biochemical Sciences, Microbiology Section, University of Perugia, Perugia, Italy.
Eva
E
Pericolini
Elena
E
Gabrielli
Elio
E
Cenci
Magdia
M
De Jesus
Francesco
F
Bistoni
Arturo
A
Casadevall
Anna
A
Vecchiarelli
D019011:Antigens, CD7 / Q000276:immunology / Q000378:metabolism*; D017209:Apoptosis / Q000276:immunology*; D015153:Blotting, Western; D053148:Caspase 3 / Q000276:immunology / Q000378:metabolism; D053178:Caspase 6 / Q000276:immunology / Q000378:metabolism; D053179:Caspase 7 / Q000276:immunology / Q000378:metabolism; D003455:Cryptococcus neoformans / Q000276:immunology; D004789:Enzyme Activation / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D019169:Jurkat Cells; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism*; D051917:Leukosialin / Q000276:immunology / Q000378:metabolism*; D011134:Polysaccharides; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D019011:Antigens, CD7; D051917:Leukosialin; D011134:Polysaccharides; D011135:Polysaccharides, Bacterial; C043689:galactoxylomannan; D017493:Leukocyte Common Antigens; D053148:Caspase 3; D053178:Caspase 6; D053179:Caspase 7