| Organ-specific innate immune responses in a mouse model of invasive candidiasis. | |
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MedLine Citation:
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PMID: 21063074 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In a fatal mouse model of invasive candidiasis (IC), fungal burden changes with variable dynamics in the kidney, brain, spleen, and liver and declines in all organs except for the kidney, which inexorably loses function. Since leukocytes are required to control Candida, we hypothesized that differential leukocyte infiltration determines organ-specific outcome of the infection. We defined leukocyte accumulation in the blood, kidney, brain, spleen, and liver after infection using fluorescent-activated cell sorting (FACS) and immunohistochemistry. Accumulation of Ly6c(int)CD11b(+) neutrophils predominated in all organs except the brain, where CD45(int)CD11b(+)CD11c(-) microglia were the major leukocytes detected, surrounding foci of invading Candida. Significantly more neutrophils accumulated in the spleen and liver than in the kidney during the first 24 h after infection, when neutrophil presence is critical for Candida control. Conversely, at later time points only the kidney continued to accumulate neutrophils, associated with immunopathology and organ failure. The distribution of neutrophils was completely different in each organ, with large abscesses exclusively forming in the kidney. Candida filamentation, an essential virulence factor, was seen in the kidney but not in the spleen or liver. IC induced Ly6c(hi)CD11b(+) inflammatory monocyte and NK1.1(+) cell expansion in the blood and all organs tested, and MHCII(+)F4/80(+)CD11c(-) macrophage accumulation, mainly in the spleen and liver. This study is the first detailed analysis of leukocyte subsets accumulating in different target organs during IC. The results delineate immune responses to the same pathogen that are highly idiosyncratic for each organ tested. The work provides novel insights into the balance between effective host defense and immunopathology in IC. |
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Authors:
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Michail S Lionakis; Jean K Lim; Chyi-Chia Richard Lee; Philip M Murphy |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural Date: 2010-11-09 |
Journal Detail:
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Title: Journal of innate immunity Volume: 3 ISSN: 1662-8128 ISO Abbreviation: J Innate Immun Publication Date: 2011 |
Date Detail:
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Created Date: 2011-02-22 Completed Date: 2011-06-17 Revised Date: 2012-02-01 |
Medline Journal Info:
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Nlm Unique ID: 101469471 Medline TA: J Innate Immun Country: Switzerland |
Other Details:
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Languages: eng Pagination: 180-99 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 S. Karger AG, Basel. |
Affiliation:
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Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Candida albicans / immunology, pathogenicity* Candidiasis, Invasive / immunology*, microbiology, pathology Cell Movement Disease Models, Animal* Female Flow Cytometry Humans Immunity, Innate* Kidney / immunology, microbiology, pathology Leukocytes / cytology, physiology Macrophages / immunology Mice Mice, Inbred C57BL Neutrophils / immunology Organ Specificity |
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