title: A critical role for FcgammaRIIB in up-regulation of Fas ligand induced by a microbial polysaccharide.
abstract: The microbial capsular polysaccharide glucuronoxylomannan (GXM) from the opportunistic fungus Cryptoccocus neoformans is able to alter the innate and adaptive immune response through multi-faceted mechanisms of immunosuppression. The ability of GXM to dampen the immune response involves the induction of T cell apoptosis, which is dependent on GXM-induced up-regulation of Fas ligand (FasL) on antigen-presenting cells. In this study we elucidate the mechanism exploited by GXM to induce up-regulation of FasL. We demonstrate that (i) the activation of FasL is dependent on GXM interaction with FcgammaRIIB (FcγRIIB); (ii) GXM induces activation of c-Jun NH(2) -terminal kinase (JNK) and p38 signal transduction pathways via FcγRIIB; (iii) this leads to downstream activation of c-Jun; (iv) JNK and p38 are simultaneously, but independently, activated; (v) FasL up-regulation occurs via JNK and p38 activation; and (vi) apoptosis occurs via FcγRIIB engagement with consequent JNK and p38 activation. Our results highlight a fast track to FasL up-regulation via FcγRIIB, and assign to this receptor a novel anti-inflammatory role that also accounts for induced peripheral tolerance. These results contribute to our understanding of the mechanism of immunosuppression that accompanies cryptococcosis.
authors: Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy.
authors: M
authors: M
authors: Piccioni
authors: C
authors: C
authors: Monari
authors: S
authors: S
authors: Bevilacqua
authors: S
authors: S
authors: Perito
authors: F
authors: F
authors: Bistoni
authors: T R
authors: TR
authors: Kozel
authors: A
authors: A
authors: Vecchiarelli
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