Capsular polysaccharides galactoxylomannan and glucuronoxylomannan from Cryptococcus neoformans induce macrophage apoptosis mediated by Fas ligand.
The effects of capsular polysaccharides, galactoxylomannan (GalXM) and glucuronoxylomannan (GXM), from acapsular (GXM negative) and encapsulate strains of Cryptococcus neoformans were investigated in RAW 264.7 and peritoneal macrophages. Here, we demonstrate that GalXM and GXM induced different cytokines profiles in RAW 264.7 macrophages. GalXM induced production of TNF-alpha, NO and iNOS expression, while GXM predominantly induced TGF-beta secretion. Both GalXM and GXM induced early morphological changes identified as autophagy and late macrophages apoptosis mediated by Fas/FasL interaction, a previously unidentified mechanism of virulence. GalXM was more potent than GXM at induction of Fas/FasL expression and apoptosis on macrophages in vitro and in vivo. These findings uncover a mechanism by which capsular polysaccharides from C. neoformans might compromise host immune responses.
Villena
Suellen N
SN
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21 944970, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, RJ, Brazil.
Pinheiro
Roberta O
RO
Pinheiro
Carla S
CS
Nunes
Marise P
MP
Takiya
Cristina M
CM
DosReis
George A
GA
Previato
José O
JO
Mendonça-Previato
Lucia
L
Freire-de-Lima
Célio G
CG
D000818:Animals; D017209:Apoptosis; D016667:Bacterial Capsules / Q000737:chemistry*; D002478:Cells, Cultured; D003453:Cryptococcosis / Q000276:immunology; D003455:Cryptococcus neoformans / Q000737:chemistry*; D053222:Fas Ligand Protein / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D011135:Polysaccharides, Bacterial / Q000302:isolation & purification / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D053222:Fas Ligand Protein; D011134:Polysaccharides; D011135:Polysaccharides, Bacterial; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C043689:galactoxylomannan; C027478:glucuronoxylomannan; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse