Capsular polysaccharides galactoxylomannan and glucuronoxylomannan from Cryptococcus neoformans induce macrophage apoptosis mediated by Fas ligand

Villena, Suellen N.; Pinheiro, Roberta Olmo; Pinheiro, Carla S.; Nunes, Marise P.; Takiya, Christina Maeda; DosReis, George A.; Previato, José O.; Mendonça-Previato, Lúcia; Freire-de-Lima, Célio Geraldo

doi:10.1111/j.1462-5822.2008.01125.x

Cited by 111 publications

(109 citation statements)

References 36 publications

Supporting

Mentioning

102

Contrasting

Unclassified

Order By: Relevance

“…Mouse Th17 differentiation occurs only in the simultaneous presence of IL-6 and TGF-␤, while IL-23 represents a growth factor rather than a differentiation factor (8). It has been previously reported that GXM is able to induce TGF-␤ in macrophages (49). In our experimental system GXM suppresses TGF-␤ in joints early after the onset of treatment.…”

Section: Discussionmentioning

confidence: 63%

See 1 more Smart Citation

A Microbial Polysaccharide Reduces the Severity of Rheumatoid Arthritis by Influencing Th17 Differentiation and Proinflammatory Cytokines Production

Monari

Bevilacqua

Piccioni

et al. 2009

The Journal of Immunology

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is a chronic and debilitating autoimmune disease characterized by chronic joint inflammation with subsequent cartilage and bone destruction. RA is emerging as a model of IL-17-driven autoimmune inflammatory disease. IL-17 is a marker for Th17 cells, with its master regulator being the retinoic acid receptor-related orphan receptor (RORγt) regulated by STAT3 signaling. Glucuronoxylomannan (GXM), a polysaccharide representing the main component of the capsular material of the opportunistic yeast Cryptococcus neoformans, exhibits potent immunosuppressive properties both in vitro and in vivo. The present study investigates the effects of GXM treatment on the progression of collagen-induced arthritis. GXM suppressed clinical signs of collagen-induced arthritis and blocked joint erosion progression. This effect was mediated by down-regulation of key cytokines involved in the pathogenesis of RA such as TNF-α and IL-1β, and up-regulation of the inhibitory cytokine IL-10. Moreover, a reduction of IL-6 and TGF-β, which inhibit Th17 differentiation with consequent decreased IL-17 production at the local and systemic level, was observed. The effect of GXM on Th17 differentiation mirrored the reduction in STAT3 activation and inhibition of RORγt synthesis. Consequently, this work highlights the beneficial properties of an efficacious compound that could eventually be destined to the clinic.

show abstract

Section: Discussionmentioning

confidence: 63%

“…This apparent discrepancy could be due to the different experimental systems used. In particular in a report from Villena et al (49) the regulation of GXM was evidenced in an in vitro system by using a macrophage cell line. This experimental condition is quite different from that used by us.…”

Section: Discussionmentioning

confidence: 99%

A Microbial Polysaccharide Reduces the Severity of Rheumatoid Arthritis by Influencing Th17 Differentiation and Proinflammatory Cytokines Production

Monari

Bevilacqua

Piccioni

et al. 2009

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…72) and also for fungal pathogens such as Cr. neoformans (24). However, we did not observe signs of apoptosis by C. glabratainfected MDMs, indicating that, at least during the early stages (24 h) of interaction, C. glabrata does not induce apoptosis.…”

Section: Escape From Macrophagesmentioning

confidence: 55%

“…Additionally, C. albicans modulates the immune response indirectly via manipulating the host's cytokine response (22,23). The capsule of Cryptococcus neoformans has been shown to mediate macrophage apoptosis and therefore induces a distinct anti-inflammatory mechanism to kill the phagocyte (24). Cr.…”

mentioning

confidence: 99%

The Facultative Intracellular Pathogen Candida glabrata Subverts Macrophage Cytokine Production and Phagolysosome Maturation

Seider

Brunke

Schild

et al. 2011

The Journal of Immunology

180

221

View full text Add to dashboard Cite

Although Candida glabrata is an important human pathogenic yeast, its pathogenicity mechanisms are largely unknown. Immune evasion strategies seem to play key roles during infection, since very little inflammation is observed in mouse models. Furthermore, C. glabrata multiplies intracellularly after engulfment by macrophages. In this study, we sought to identify the strategies that enable C. glabrata to survive phagosome biogenesis and antimicrobial activities within human monocyte-derived macrophages. We show that, despite significant intracellular proliferation, macrophage damage or apoptosis was not apparent, and production of reactive oxygen species was inhibited. Additionally, with the exception of GM-CSF, levels of pro- and anti-inflammatory cytokines were only marginally increased. We demonstrate that adhesion to and internalization by macrophages occur within minutes, and recruitment of endosomal early endosomal Ag 1 and lysosomal-associated membrane protein 1 indicates phagosome maturation. However, phagosomes containing viable C. glabrata, but not heat-killed yeasts, failed to recruit cathepsin D and were only weakly acidified. This inhibition of acidification did not require fungal viability, but it had a heat-sensitive surface attribute. Therefore, C. glabrata modifies the phagosome into a nonacidified environment and multiplies until the host cells finally lyse and release the fungi. Our results suggest persistence of C. glabrata within macrophages as a possible immune evasion strategy.

show abstract

“…GXM is the more abundant capsule component; cells without it are acapsular and are avirulent in animal models of cryptococcal infection (28). GXMGal comprises less of the capsule mass but also exhibits potent immunomodulatory properties (32)(33)(34)(35)(36) and may regulate capsule expansion (37).…”

mentioning

confidence: 99%

Unusual Galactofuranose Modification of a Capsule Polysaccharide in the Pathogenic Yeast Cryptococcus neoformans

Heiß

Skowyra

Liu

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Galactofuranose, the five-membered ring form of galactose, occurs in the encapsulated pathogenic fungus Cryptococcus neoformans but not in humans. Results: We established the position of galactofuranose within a capsule polysaccharide and characterized cryptococci lacking this modification. Conclusion: Galactofuranose occurs in an unusual linkage but is not required for growth or virulence. Significance: This work fills a gap in knowledge about a pathogen-specific modification.

show abstract

Capsular polysaccharides galactoxylomannan and glucuronoxylomannan from Cryptococcus neoformans induce macrophage apoptosis mediated by Fas ligand

Cited by 111 publications

References 36 publications

A Microbial Polysaccharide Reduces the Severity of Rheumatoid Arthritis by Influencing Th17 Differentiation and Proinflammatory Cytokines Production

A Microbial Polysaccharide Reduces the Severity of Rheumatoid Arthritis by Influencing Th17 Differentiation and Proinflammatory Cytokines Production

The Facultative Intracellular Pathogen Candida glabrata Subverts Macrophage Cytokine Production and Phagolysosome Maturation

Unusual Galactofuranose Modification of a Capsule Polysaccharide in the Pathogenic Yeast Cryptococcus neoformans

Contact Info

Product

Resources

About