early-expressed chemokines predict kidney immunopathology in experimental disseminated candida albicans infectionsearly-expressed趋化因子预测肾脏免疫病理实验传播白色念珠菌感染.pdfVIP

Early-Expressed Chemokines Predict Kidney Immunopathology in Experimental Disseminated Candida albicans Infections Donna M. MacCallum, Luis Castillo, Alistair J. P. Brown, Neil A. R. Gow, Frank C. Odds* 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-1b, MCP-1, KC, IL-6, G-CSF, TNF, MIP-2 and MIP- 1b, 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-1b 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. a