Cryptococcus neoformans capsular polysaccharide component galactoxylomannan induces apoptosis of human T-cells through activation of caspase-8.
The major virulence factor of Cryptococcus neoformans is its polysaccharide capsule composed of glucuronoxylomannan (GXM), galactoxylomannan (GalXM) and mannoproteins. A variety of immunomodulating activities have been described for GXM and mannoproteins but little is known about possible interactions of GalXM with the immune system. In the present article, we investigate the effect of purified soluble GalXM on human T lymphocytes. The results indicate that, GalXM (i) can affect selected immune responses; (ii) causes significant impairment of T cell proliferation and increases interferon-gamma and interleukin-10 production; and (iii) induces apoptosis of T lymphocytes through activation of caspase-8 that terminates with fragmentation of DNA. These results are the first to suggest a role for GalXM in C. neoformans virulence by demonstrating that it can target human T cells, and that it may impair the development of an effective specific T cell response.
Pericolini
Eva
E
Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
Cenci
Elio
E
Monari
Claudia
C
De Jesus
Magdia
M
Bistoni
Francesco
F
Casadevall
Arturo
A
Vecchiarelli
Anna
A
D017209:Apoptosis; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism*; D049109:Cell Proliferation; D003455:Cryptococcus neoformans / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects; D004789:Enzyme Activation; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis; D019169:Jurkat Cells; D011134:Polysaccharides / Q000494:pharmacology / Q000502:physiology; D011135:Polysaccharides, Bacterial / Q000494:pharmacology / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*
D011134:Polysaccharides; D011135:Polysaccharides, Bacterial; D016753:Interleukin-10; C043689:galactoxylomannan; C027478:glucuronoxylomannan; D007371:Interferon-gamma; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases