Dataset Information

Early-expressed chemokines predict kidney immunopathology in experimental disseminated Candida albicans infections.

ABSTRACT:

Background

The mouse intravenous challenge model of Candida albicans infection is widely used to determine aspects of host-fungus interaction. We investigated the production of cytokines in the kidneys and spleen of animals up to 48 h after challenge with virulent and attenuated isolates and related these responses to semi-quantitative estimations of histopathological changes in the kidney.

Methodology/principal findings

Progression of Candida albicans infection of the kidney in response to highly virulent fungal strains was characterized by higher levels of host cellular infiltrate, higher lesion densities and greater quantities of fungal elements at 24 and 48 h, and by higher kidney concentrations of IL-1beta, MCP-1, KC, IL-6, G-CSF, TNF, MIP-2 and MIP-1beta, among the immune effectors measured. Levels of the chemokine KC as early as 12 h after challenge correlated significantly with all later measurements of lesion severity. Early renal IL-6 and MIP-1beta concentrations also correlated with subsequent damage levels, but less significantly than for KC. All chemokines tested appeared in kidney homogenates, while most of the cytokines were undetectable in kidney and spleen homogenates. GM-CSF and IL-10 showed inverse correlations with measures of lesion severity, suggesting these alone may have exerted a defensive role. Spleen levels of KC at all times showed significant associations with kidney lesion measurements.

Conclusions/significance

Elevated chemokine levels, including KC, represent the earliest responses to C. albicans infection in the mouse kidney. Fungal strains of low mouse virulence stimulate a lower innate response and less host infiltrate than more virulent strains. These findings are consistent with immunopathological damage to kidneys in the mouse C. albicans infection model and with growing evidence implicating some TLR pathways as the main point of interaction between fungal surface polysaccharides and leukocytes.

SUBMITTER: MacCallum DM

PROVIDER: S-EPMC2712765 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Publications

Early-expressed chemokines predict kidney immunopathology in experimental disseminated Candida albicans infections.

MacCallum Donna M DM Castillo Luis L Brown Alistair J P AJ Gow Neil A R NA Odds Frank C FC

PloS one 20090729 7

<h4>Background</h4>The mouse intravenous challenge model of Candida albicans infection is widely used to determine aspects of host-fungus interaction. We investigated the production of cytokines in the kidneys and spleen of animals up to 48 h after challenge with virulent and attenuated isolates and related these responses to semi-quantitative estimations of histopathological changes in the kidney.<h4>Methodology/principal findings</h4>Progression of Candida albicans infection of the kidney in r ...[more]

PMID: 19641609

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Project description:ObjectiveThe aims of this study were as follows. First, we sought to compare the in vitro susceptibility of liposomal amphotericin B (LAmB) and anidulafungin on Candida albicans and Candida glabrata biofilms growing on silicone discs. Second, we sought to compare the activity of LAmB versus anidulafungin for the treatment of experimental catheter-related C. albicans and C. glabrata infections with the antifungal lock technique in a rabbit model.MethodsTwo C. albicans and two C. glabrata clinical strains were used. The minimum biofilm eradication concentration for 90% eradication (MBEC90) values were determined after 48h of treatment with LAmB and anidulafungin. Confocal microscopy was used to visualize the morphology and viability of yeasts growing in biofilms. Central venous catheters were inserted into New Zealand rabbits, which were inoculated of each strain of C. albicans and C. glabrata. Then, catheters were treated for 48h with saline or with antifungal lock technique using either LAmB (5mg/mL) or anidulafungin (3.33mg/mL).ResultsIn vitro: anidulafungin showed greater activity than LAmB against C. albicans and C. glabrata strains. For C. albicans: MBEC90 of anidulafungin versus LAmB: CA176, 0.03 vs. 128 mg/L; CA180, 0.5 vs. 64 mg/L. For C. glabrata: MBEC90 of anidulafungin versus LAmB: CG171, 0.5 vs. 64 mg/L; CG334, 2 vs. 32 mg/L. In vivo: for C. albicans species, LAmB and anidulafungin achieved significant reductions relative to growth control of log10 cfu recovered from the catheter tips (CA176: 3.6±0.3 log10 CFU, p?0.0001; CA180: 3.8±0.1 log10 CFU, p?0.01). For C. glabrata, anidulafungin lock therapy achieved significant reductions relative to the other treatments (CG171: 4.8 log10 CFU, p?0.0001; CG334: 5.1 log10 CFU, p?0.0001).ConclusionsFor the C. albicans strains, both LAmB and anidulafungin may be promising antifungal lock technique for long-term catheter-related infections; however, anidulafungin showed significantly higher activity than LAmB against the C. glabrata strains.

Dataset Information

Early-expressed chemokines predict kidney immunopathology in experimental disseminated Candida albicans infections.

Background

Methodology/principal findings

Conclusions/significance

Publications

Early-expressed chemokines predict kidney immunopathology in experimental disseminated Candida albicans infections.

Similar Datasets

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