Taxonomic group: fungi / Basidiomycota
(Phylum: Basidiomycota)
Associated disease: infection due to Cryptococcus neoformans [ICD11:
XN3EH 
]
NCBI PubMed ID: 21605112Publication DOI: 10.1111/j.1365-2249.2011.04415.xJournal NLM ID: 0057202Publisher: Oxford: Blackwell Scientific Publications
Correspondence: vecchiar
unipg.it
Institutions: Microbiology Section, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy, Department of Microbiology and Immunology, University of Nevada, Reno, USA
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.
capsular polysaccharides, apoptosis, signal transduction, Fc receptors, monocytes/macrophages
Structure type: suggested polymer biological repeating unit
Location inside paper: fig. 8, GXM
Trivial name: glucuronoxylomannan (GXM)
Compound class: CPS, EPS, O-polysaccharide, O-antigen, cell wall polysaccharide, polysaccharide, glucuronoxylomannan, capsule polysaccharide
Contained glycoepitopes: IEDB_114701,IEDB_115136,IEDB_115576,IEDB_130701,IEDB_140116,IEDB_140630,IEDB_144983,IEDB_145668,IEDB_152206,IEDB_164174,IEDB_167188,IEDB_174332,IEDB_2270799,IEDB_423153,IEDB_76933,IEDB_983930,SB_197,SB_44,SB_67,SB_72
Methods: flow cytometry analysis, ethanol precipitation
Biological activity: GXM reduces the activity of antigen-presenting cells. It promotes apoptosis of T cells, T cell proliferation inhibition and dampening of T helper type 1 response. GXM induces up-regulation of the death receptor FasL in GXM-loaded macrophages and these cells induce apoptosis of activated T cells and Jurkat T cells via the FasL/Fas pathway.
Comments, role: chemical repeating unit frame was shifted in annotation for compatibility with structures elucidated by MS [Eukaryotic Cell 2007, 6: 1464-1473]
Related record ID(s): 4685, 40727, 40735, 41740, 41809, 41819, 42199, 113471
NCBI Taxonomy refs (TaxIDs): 178876Reference(s) to other database(s): GTC:G75580HK, CCSD:
50376, CBank-STR:15059
Show glycosyltransferases
There is only one chemically distinct structure:
Found 
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(later renamed to: Cryptococcus neoformans var. grubii CN6)