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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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Time course of concentrations (ng/g) of KC, RANTES and GM-CSF in kidney and spleen samples from mice infected with 11 different C. albicans strains.Details as in Fig. 4.
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pone-0006420-g005: Time course of concentrations (ng/g) of KC, RANTES and GM-CSF in kidney and spleen samples from mice infected with 11 different C. albicans strains.Details as in Fig. 4.

Mentions: Figs. 4 and 5 show the concentrations of the most abundant chemokines and cytokines in organ samples at 12, 24 and 48 h. Chemokines MCP-1 (Fig. 4), MIG (Fig. 4), and KC (Fig. 5) were abundant in samples from infected kidneys by 12 h after challenge. MIG was the most abundant chemokine at all time intervals in kidney samples (Fig. 4). However, while levels of KC and MCP-1 tended to rise in kidneys of mice infected with all 11 strains over the 48 h period of measurement, MIG levels rose between 24 h and 48 h only for animals infected with J990102, SC5314 and pmr1/PMR1. For the remaining isolates MIG concentrations were similar at 24 and 48 h or fell from a peak at 24 h (Fig. 4). Detectable levels of GM-CSF were measured at 12 h for some kidney samples (Fig. 5), but they remained low (below 100 pg/g on average) throughout the time course of the experiment with the exception of the 48 h kidneys from mice infected with pmr1/PMR1.


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)

Time course of concentrations (ng/g) of KC, RANTES and GM-CSF in kidney and spleen samples from mice infected with 11 different C. albicans strains.Details as in Fig. 4.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2712765&req=5

pone-0006420-g005: Time course of concentrations (ng/g) of KC, RANTES and GM-CSF in kidney and spleen samples from mice infected with 11 different C. albicans strains.Details as in Fig. 4.
Mentions: Figs. 4 and 5 show the concentrations of the most abundant chemokines and cytokines in organ samples at 12, 24 and 48 h. Chemokines MCP-1 (Fig. 4), MIG (Fig. 4), and KC (Fig. 5) were abundant in samples from infected kidneys by 12 h after challenge. MIG was the most abundant chemokine at all time intervals in kidney samples (Fig. 4). However, while levels of KC and MCP-1 tended to rise in kidneys of mice infected with all 11 strains over the 48 h period of measurement, MIG levels rose between 24 h and 48 h only for animals infected with J990102, SC5314 and pmr1/PMR1. For the remaining isolates MIG concentrations were similar at 24 and 48 h or fell from a peak at 24 h (Fig. 4). Detectable levels of GM-CSF were measured at 12 h for some kidney samples (Fig. 5), but they remained low (below 100 pg/g on average) throughout the time course of the experiment with the exception of the 48 h kidneys from mice infected with pmr1/PMR1.

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