Immunosuppression, interleukin‐10 synthesis and apoptosis are induced in rats inoculated with <i>Cryptococcus neoformans</i> glucuronoxylomannan

Chiapello, Laura S.; Baronetti, José L.; Aoki, María Pilar; Gea, Susana; Rubinstein, H.R.; Masih, Diana T.

doi:10.1111/j.1365-2567.2004.01970.x

Cited by 35 publications

(23 citation statements)

References 60 publications

(147 reference statements)

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“…Exposure of macrophages to vesicle preparations resulted in enhanced levels of IL-10 and TGF-␤, anti-inflammatory cytokines whose production is positively modulated by the vesicular component GXM (11,42). In agreement with the role of GXM in the upregulation of IL-10, CAP67 vesicles induced a significantly lower amount of this cytokine, although the level was significantly greater than in untreated macrophages.…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles from Cryptococcus neoformans Modulate Macrophage Functions

Oliveira¹,

et al. 2010

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Cryptococcus neoformans and distantly related fungal species release extracellular vesicles that traverse the cell wall and contain a varied assortment of components, some of which have been associated with virulence. Previous studies have suggested that these extracellular vesicles are produced in vitro and during animal infection, but the role of vesicular secretion during the interaction of fungi with host cells remains unknown. In this report, we demonstrate by fluorescence microscopy that mammalian macrophages can incorporate extracellular vesicles produced by C. neoformans. Incubation of cryptococcal vesicles with murine macrophages resulted in increased levels of extracellular tumor necrosis factor alpha (TNF-␣), interleukin-10 (IL-10), and transforming growth factor ␤ (TGF-␤). Vesicle preparations also resulted in a dose-dependent stimulation of nitric oxide production by phagocytes, suggesting that vesicle components stimulate macrophages to produce antimicrobial compounds. Treated macrophages were more effective at killing C. neoformans yeast. Our results indicate that the extracellular vesicles of C. neoformans can stimulate macrophage function, apparently activating these phagocytic cells to enhance their antimicrobial activity. These results establish that cryptococcal vesicles are biologically active.

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Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles from Cryptococcus neoformans Modulate Macrophage Functions

Oliveira¹,

et al. 2010

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“…grubii, which has been used in previous studies. 6,[20][21][22][23] To perform the experiments, living yeasts of C. neoformans were expanded in liquid Sabouraud media for 24 hr in a gyratory shaker at 30°. Then, the yeasts were washed three times with phosphate-buffered saline (PBS), resuspended at 10 7 cells/ml and opsonized with 5 lg/ml of mAb 3C2 for 30 min at 37°.…”

Section: Neoformansmentioning

confidence: 99%

Rat eosinophils stimulate the expansion of Cryptococcus neoformans-specific CD4+ and CD8+ T cells with a T-helper 1 profile

et al. 2010

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Summary Experimental Cryptococcus neoformans infection in rats has been shown to have similarities with human cryptococcosis, revealing a strong granulomatous response and a low susceptibility to dissemination. Moreover, it has been shown that eosinophils are components of the inflammatory response to C. neoformans infections. In this in vitro study, we demonstrated that rat peritoneal eosinophils phagocytose opsonized live yeasts of C. neoformans, and that the phenomenon involves the engagement of FcγRII and CD18. Moreover, our results showed that the phagocytosis of opsonized C. neoformans triggers eosinophil activation, as indicated by (i) the up‐regulation of major histocompatibility complex (MHC) class I, MHC class II and costimulatory molecules, and (ii) an increase in interleukin (IL)‐12, tumour necrosis factor‐α (TNF‐α) and interferon‐γ (IFN‐γ) production. However, nitric oxide (NO) and hydrogen peroxide (H2O2) synthesis by eosinophils was down‐regulated after interaction with C. neoformans. Furthermore, this work demonstrated that CD4+ and CD8+ T lymphocytes isolated from spleens of infected rats and cultured with C. neoformans‐pulsed eosinophils proliferate in an MHC class II‐ and class I‐dependent manner, respectively, and produce important amounts of T‐helper 1 (Th1) type cytokines, such as TNF‐α and IFN‐γ, in the absence of T‐helper 2 (Th2) cytokine synthesis. In summary, the present study demonstrates that eosinophils act as fungal antigen‐presenting cells and suggests that C. neoformans‐loaded eosinophils might participate in the adaptive immune response.

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“…Lungs were then excised, weighed, and macerated in PBS with a cell strainer for cytokine determination using the DuoSet ELISA development system kit (R&D System). Interleukins 17 and 10 (IL-17 and IL-10) and tumor necrosis factor alpha (TNF-␣) were chosen as the prototypes for cytokine tests based on previous literature on the anticryptococcal immunity (11,32) and chitin-induced cellular responses (15,16). Cytokine contents were normalized to the mass of lungs removed from each animal.…”

Section: Methodsmentioning

confidence: 99%

Chitin-Like Molecules Associate with Cryptococcus neoformans Glucuronoxylomannan To Form a Glycan Complex with Previously Unknown Properties

et al. 2012

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ABSTRACTIn prior studies, we demonstrated that glucuronoxylomannan (GXM), the major capsular polysaccharide of the fungal pathogenCryptococcus neoformans, interacts with chitin oligomers at the cell wall-capsule interface. The structural determinants regulating these carbohydrate-carbohydrate interactions, as well as the functions of these structures, have remained unknown. In this study, we demonstrate that glycan complexes composed of chitooligomers and GXM are formed during fungal growth and macrophage infection byC. neoformans. To investigate the required determinants for the assembly of chitin-GXM complexes, we developed a quantitative scanning electron microscopy-based method using different polysaccharide samples as inhibitors of the interaction of chitin with GXM. This assay revealed that chitin-GXM association involves noncovalent bonds and large GXM fibers and depends on theN-acetyl amino group of chitin. Carboxyl andO-acetyl groups of GXM are not required for polysaccharide-polysaccharide interactions. Glycan complex structures composed of cryptococcal GXM and chitin-derived oligomers were tested for their ability to induce pulmonary cytokines in mice. They were significantly more efficient than either GXM or chitin oligomers alone in inducing the production of lung interleukin 10 (IL-10), IL-17, and tumor necrosis factor alpha (TNF-α). These results indicate that association of chitin-derived structures with GXM through theirN-acetyl amino groups generates glycan complexes with previously unknown properties.

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Immunosuppression, interleukin‐10 synthesis and apoptosis are induced in rats inoculated with Cryptococcus neoformans glucuronoxylomannan

Cited by 35 publications

References 60 publications

Extracellular Vesicles from Cryptococcus neoformans Modulate Macrophage Functions

Extracellular Vesicles from Cryptococcus neoformans Modulate Macrophage Functions

Rat eosinophils stimulate the expansion of Cryptococcus neoformans-specific CD4+ and CD8+ T cells with a T-helper 1 profile

Chitin-Like Molecules Associate with Cryptococcus neoformans Glucuronoxylomannan To Form a Glycan Complex with Previously Unknown Properties

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