At low serum glucan concentrations there is an inverse correlation between serum glucan and serum cytokine levels in ICU patients with infections

Gonzalez, J.Andres; Digby, Justin; Rice, Peter J.; Breuel, Kevin F.; DePonti, W.Keith; Kalbfleisch, John H.; Browder, I. William; Williams, David L.

doi:10.1016/j.intimp.2004.05.010

Cited by 5 publications

(4 citation statements)

References 16 publications

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“…However, recent evidence indicates that serum glucan levels are elevated in patients infected by bacteria that do not produce glucans (Digby et al, 2003). Even more perplexing was the observation that normal or control patients had low (Յ20 pg/ml), but detectable, levels of serum glucan (Digby et al, 2003;Gonzalez et al, 2004). Our data indicate that soluble glucans can translocate from the GI tract into the systemic circulation in normal rats.…”

Section: Discussionmentioning

confidence: 50%

“…Finally, numerous studies have demonstrated that glucans are found in the systemic circulation of patients with fungal infections (Digby et al, 2003;Gonzalez et al, 2004). Since glucans are evolutionarily conserved in microbes, it has been assumed that blood-borne glucans in the infected patient are derived entirely from pathogens (Digby et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

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Oral Delivery and Gastrointestinal Absorption of Soluble Glucans Stimulate Increased Resistance to Infectious Challenge

Rice

Adams²,

Ozment-Skelton³

et al. 2005

J Pharmacol Exp Ther

284

233

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Glucans are immunomodulatory carbohydrates found in the cell walls of fungi and certain bacteria. We examined the pharmacokinetics of three water-soluble glucans (glucan phosphate, laminarin, and scleroglucan) after oral administration of 1 mg/kg doses in rats. Maximum plasma concentrations for glucan phosphate occurred at 4 h. In contrast, laminarin and scleroglucan showed two plasma peaks between 0.5 and 12 h. At 24 h, 27 Ϯ 3% of the glucan phosphate and 20 Ϯ 7% of the laminarin remained in the serum. Scleroglucan was rapidly absorbed and eliminated. The liver did not significantly contribute to the clearance of plasma glucan. Biological effects were further studied in mice. Following oral administration of 1 mg, glucans were bound and internalized by intestinal epithelial cells and gut-associated lymphoid tissue (GALT) cells. Internalization of glucan by intestinal epithelial cells was not Dectindependent. GALT expression of Dectin-1 and toll-like receptor (TLR) 2, but not TLR4, increased following oral administration of glucan. Oral glucan increased systemic levels of interleukin (IL)-12 (151 Ϯ 15%) in mice. Oral glucan administration also increased survival in mice challenged with Staphylococcus aureus or Candida albicans. These data demonstrate that orally administered water-soluble glucans translocate from the gastrointestinal (GI) tract into the systemic circulation. The glucans are bound by GI epithelial and GALT cells, and they modulate the expression of pattern recognition receptors in the GALT, increase IL-12 expression, and induce protection against infectious challenge.

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Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Oral Delivery and Gastrointestinal Absorption of Soluble Glucans Stimulate Increased Resistance to Infectious Challenge

Rice

Adams²,

Ozment-Skelton³

et al. 2005

J Pharmacol Exp Ther

284

233

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“…The soluble form is produced when macrophages recognize fungal surfaces and release enzymes that degrade cell wall glucans [47, 48]. These soluble glucans are commonly found in circulation in the serum of patients with fungal infections [49, 50]. β-glucans possess three different structures: low molecular weights possess a random coil structure while high molecular weight glucans possess either a single or triple helical structure [66].…”

Section: Discussionmentioning

confidence: 99%

Dectin-1 Molecular Aggregation and Signaling is Sensitive to β-Glucan Structure and Glucan Exposure on Candida albicans Cell Walls

Anaya

Wester

et al. 2019

Preprint

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Candidemia is the most common bloodstream infection in the United States. During 23 infection, the fungal cell wall is an important virulence factor, playing roles in adhesion, 24 immune recognition and colonization. The human innate immune system recognizes β-25 glucan, a highly immunogenic component of the fungal cell wall. During innate immune 26 recognition of Candida, the organization of cell wall β-glucan is an important 27 determinant of a successful immune activation. However, there have been many reports 28 showing conflicting biological activities of β-glucans with different size, branching and 29 structure. Here, using quantitative fluorescence imaging techniques, we investigate how 30 differential size and structure of β-glucan impacts activation of the innate immune 31 receptor, Dectin-1A. Our results indicate a positive correlation between highly structured 32 glucans and Dectin-1A activation. Furthermore, we determined this is due to the higher 33 ordered β-glucan causing Dectin-1A receptors to form aggregates that are below 15 nm 34 in size. Finally, Dectin-1A receptor aggregation has also been shown to form at fungal 35 particle contact sites with high β-glucan exposure. 36 Abstract 37Dectin-1A is a C-type Lectin innate immunoreceptor that recognizes β-(1,3:1,6)-glucan, 38 a structural component of Candida species cell walls. The higher order structure of β-39 glucans ranges from random coil to insoluble fiber due to varying degrees of tertiary 40 (helical) and quaternary structure. Model Saccharomyces cerevisiae β-glucans of 41 medium and high molecular weight (MMW and HMW, respectively) are highly 42 structured. In contrast, low MW glucan (LMW) is much less structured. Despite similar 43 affinity for Dectin-1A, the ability of glucans to induce Dectin-1A mediated calcium influx 3 44and Syk phosphorylation positively correlates with their degree of higher order structure. 45Chemical denaturation and renaturation of MMW glucan showed that glucan structure 46 determines agonistic potential, but not binding affinity, for Dectin-1A. We explored the 47 6 113 ITAM domains poorly recruit and activate Syk for downstream signaling [44], suggesting 114 that hemITAM domains with their single phosphotyrosine site would be poorly activating 115 in a monomeric configuration. Consistent with this hypothesis, another (hem)ITAM 116 bearing receptor, CLEC-2, is reported to require dimerization for its signaling [45]. By 117 analogy to this and other (hem)ITAM receptors, it is hypothesized that Dectin-1A must 118 oligomerize to recapitulate a multivalent binding site for Syk and to facilitate signal 119 transduction [8,45,46]. However, this prediction has not been directly explored for 120Dectin-1A in live cells at the molecular level with relation to structural determinants of 121 receptor-ligand complex organization and signaling outcomes. 122In this study, we propose that factors that induce an aggregated membrane organization 123 of Dectin-1A during activation are very important for determining signaling ...

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“…However, the consequent fall in IL-10 levels at T8 can be explained by all available cell receptors being occupied, which prevented the β-glucan linking to these receptors. Studies have demonstrated that β-glucans are recognized by receptors on the surface of cells such as macrophages, neutrophils, NK cells, dendritric cells, and fibroblasts (5,6,23).…”

Section: Discussionmentioning

confidence: 99%

Measurement of IL-10 serum levels in BALB/c mice treated with beta-1,3 polyglucose or sulfadiazine and acutely infected by Toxoplasma gondii

Picka¹,

Calvi²,

Lima³

et al. 2005

J. Venom. Anim. Toxins incl. Trop. Dis

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Acute infection by Toxoplasma gondii leads to suppression of cell-mediated immunity, facilitating chronic infection. One of the causes of immunosuppression is Interleukin-10 (IL-10) production. Glucan is used to stimulate phagocytosis. Our objective was to study IL-10 induction in male BALB/c mice with acute T. gondii BTU-2 strain infection, glucan immunostimulation, and sulfadiazine treatment. Animals were distributed into 7 groups: G1: infected with T. gondii; G2: infected with T. gondii and treated with sulfadiazine; G3: infected with T. gondii and immunostimulated with glucan; G4: infected with T. gondii, immunostimulated with glucan, and treated with sulfadiazine; G5: imunostimulated with glucan; G6: treated with saline; and G7: treated with sulfadiazine. IL-10 levels were determined by ELISA; the highest levels were found in G2, G3 and G4, and the lowest in G1 (p<0.001). Groups G1 to G5 and G7 had substantially higher levels than G6 (p<0.001). In this study, the highest IL-10 levels were found in groups treated with glucan

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At low serum glucan concentrations there is an inverse correlation between serum glucan and serum cytokine levels in ICU patients with infections

Cited by 5 publications

References 16 publications

Oral Delivery and Gastrointestinal Absorption of Soluble Glucans Stimulate Increased Resistance to Infectious Challenge

Oral Delivery and Gastrointestinal Absorption of Soluble Glucans Stimulate Increased Resistance to Infectious Challenge

Dectin-1 Molecular Aggregation and Signaling is Sensitive to β-Glucan Structure and Glucan Exposure on Candida albicans Cell Walls

Measurement of IL-10 serum levels in BALB/c mice treated with beta-1,3 polyglucose or sulfadiazine and acutely infected by Toxoplasma gondii

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