Immunosuppression, IL-10 synthesis and apoptosis are induced in rats inoculated with Cryptococcus neoformans glucuronoxylomanan

CHIAPELLO L; BARONETTI J; AOKI MP; GEA S; RUBINSTEIN HR; MASIH DT

IMMUNOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2004 vol. 113 p. 392 - 400

0019-2805

Glucuronoxylomannan (GXM) is the major Cryptococcus neoformans capsular polysaccharideand represents the main virulence factor of this fungus. In in vitro studies we have demonstratedpreviously that this acidic and high-molecular-weight polysaccharide suppresses lymphoproliferation,modulates cytokine production and promotes apoptosis in spleen mononuclear (Spm)cells from rats. In this study we demonstrate that these phenomena also occur in vivo afterthe intracardiac inoculation of GXM into normal Wistar rats. The results of this study showsuppression of the proliferative response Spm cells to concanavalin A (Con A) or heat-killedC. neoformans (HKCn) in the first 2 weeks after polysaccharide administration. In addition,increased levels of interleukin (IL)-10 were produced by Con A-stimulated Spm cells, coincidingwith immunohistochemical GXM detection in the white pulp of spleen. In particular, highproduction of IL-10 with diminution of IL-2, interferon (IFN)-c and tumour necrosis factor(TNF)-a synthesis were detected 14 days after GXM administration. In situ cell death detectionby TdT-mediated biotin?dUTP nick-end labelling (TUNEL) reaction in sections of spleen, lungand liver demonstrates apoptosis in tissues with deposits of GXM. These data demonstrate thein vivo ability of GXM to modify cytokine synthesis by Spm cells and to promote host cellapoptosis