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

MacCallum DM, Castillo L, Brown AJ, Gow NA, Odds FC - PLoS ONE (2009)

Bottom Line: 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.Spleen levels of KC at all times showed significant associations with kidney lesion measurements.

View Article: PubMed Central - PubMed

Affiliation: Aberdeen Fungal Group, Institute of Medical Sciences, Aberdeen, United Kingdom.

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.

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Scatterplots of lesion parameters.Each point represents the result for a single animal, with 3 animals per C. albicans isolate. In each figure the solid line is the regression line and the dashed curves indicate the 95% confidence region. (a) Lesion density (48 h) vs. C. albicans kidney burdens (48 h). (b) Lesion density (48 h) vs. infiltrate density(48 h). (c) C. albicans pixel density (24 h) vs. infiltrate pixel density (24 h). (d) C. albicans pixel density (48 h) vs. infiltrate pixel density (48 h).
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pone-0006420-g003: Scatterplots of lesion parameters.Each point represents the result for a single animal, with 3 animals per C. albicans isolate. In each figure the solid line is the regression line and the dashed curves indicate the 95% confidence region. (a) Lesion density (48 h) vs. C. albicans kidney burdens (48 h). (b) Lesion density (48 h) vs. infiltrate density(48 h). (c) C. albicans pixel density (24 h) vs. infiltrate pixel density (24 h). (d) C. albicans pixel density (48 h) vs. infiltrate pixel density (48 h).

Mentions: Fig. 3 shows examples of strong and weak cross-associations between the data obtained by measurements of lesion parameters for kidneys infected with 11 isolates of C. albicans. The data available from measurements at 24 and 48 h generated 36 scatterplots of the types illustrated in Fig. 3, by inclusion of 12 h viable burden data. These are summarized in Table 2 as cross-tabulations of correlations between the various measurements of kidney lesion histopathology and fungal burdens for animals infected with the 11 C. albicans strains. The correlations between the lesion parameters often reached statistical significance (Table 2). Overall, the results in Table 2 show that infection with the most virulent strains (Table 1) generated more lesions, more host infiltrate and greater quantities of fungal material, viable or not, than infection with the least virulent strains.


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

MacCallum DM, Castillo L, Brown AJ, Gow NA, Odds FC - PLoS ONE (2009)

Scatterplots of lesion parameters.Each point represents the result for a single animal, with 3 animals per C. albicans isolate. In each figure the solid line is the regression line and the dashed curves indicate the 95% confidence region. (a) Lesion density (48 h) vs. C. albicans kidney burdens (48 h). (b) Lesion density (48 h) vs. infiltrate density(48 h). (c) C. albicans pixel density (24 h) vs. infiltrate pixel density (24 h). (d) C. albicans pixel density (48 h) vs. infiltrate pixel density (48 h).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2712765&req=5

pone-0006420-g003: Scatterplots of lesion parameters.Each point represents the result for a single animal, with 3 animals per C. albicans isolate. In each figure the solid line is the regression line and the dashed curves indicate the 95% confidence region. (a) Lesion density (48 h) vs. C. albicans kidney burdens (48 h). (b) Lesion density (48 h) vs. infiltrate density(48 h). (c) C. albicans pixel density (24 h) vs. infiltrate pixel density (24 h). (d) C. albicans pixel density (48 h) vs. infiltrate pixel density (48 h).
Mentions: Fig. 3 shows examples of strong and weak cross-associations between the data obtained by measurements of lesion parameters for kidneys infected with 11 isolates of C. albicans. The data available from measurements at 24 and 48 h generated 36 scatterplots of the types illustrated in Fig. 3, by inclusion of 12 h viable burden data. These are summarized in Table 2 as cross-tabulations of correlations between the various measurements of kidney lesion histopathology and fungal burdens for animals infected with the 11 C. albicans strains. The correlations between the lesion parameters often reached statistical significance (Table 2). Overall, the results in Table 2 show that infection with the most virulent strains (Table 1) generated more lesions, more host infiltrate and greater quantities of fungal material, viable or not, than infection with the least virulent strains.

Bottom Line: 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.Spleen levels of KC at all times showed significant associations with kidney lesion measurements.

View Article: PubMed Central - PubMed

Affiliation: Aberdeen Fungal Group, Institute of Medical Sciences, Aberdeen, United Kingdom.

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.

Show MeSH
Related in: MedlinePlus