title: Glucuronoxylomannan of Cryptococcus neoformans exacerbates in vitro yeast cell growth by interleukin 10-dependent inhibition of CD4+ T lymphocyte responses.
abstract: Glucuronoxylomannan (GXM), the major capsular polysaccharide of Cryptococcus neoformans, is the most important virulence factor of this fungus. We analyzed the molecular events related to protective immune responses against a non-encapsulated strain of C. neoformans, mediated by murine splenic CD4(+) T lymphocytes in vitro, and the impact of GXM addition upon these events. Both the lymphoproliferation of CD4(+) T cells and the control of fungus growth were dependent on B7 co-stimulation. Addition of GXM did not modify CD4(+) T cell proliferation, but exacerbated infection in cultures obtained from normal and infected hosts. GXM enhanced the secretion of IL-10 and IL-4, while it reduced the production of pro-inflammatory cytokines TNF-alpha and IFN-gamma. The blockade of IL-10 activity with neutralizing antibodies increased TNF-alpha production and reduced yeast cell growth. The findings suggest that GXM exacerbates infection by down-regulating cell-mediated protective immune response and that IL-10 is implicated in yeast evasion.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Regis
authors.initials: R
authors.lastname: Mariano Andrade
authors.forename: Geisy
authors.initials: G
authors.lastname: Monteiro Almeida
authors.forename: George
authors.initials: G
authors.lastname: Alexandre DosReis
authors.forename: Cleonice
authors.initials: C
authors.lastname: Alves Melo Bento
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D003455:Cryptococcus neoformans / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000502:physiology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011134:Polysaccharides / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015003:Yeasts / Q000254:growth & development*
chemical_list: D018122:B7-1 Antigen; D011134:Polysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C027478:glucuronoxylomannan; D007371:Interferon-gamma