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 Ly6cintCD11b+ neutrophils predominated in all organs except the brain, where CD45intCD11b+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 Ly6chiCD11b+ 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.
© 2010 S. Karger AG, Basel
- Cellular immunology
- Flow cytometry
- Leukocyte trafficking
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Dr. Philip M. Murphy
Molecular Signaling Section, Laboratory of Molecular Immunology
National Institutes of Health, Building 10, Room 11N113, 9000 Rockville Pike
Bethesda, MD 20892 (USA)
Tel. +1 301 496 8616, Fax +1 301 402 4369, E-Mail firstname.lastname@example.org
Presented in part at the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, September 12–15, 2009 (late-breaker abstract M-1696b) and at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy, Boston, September 12–15, 2010 (abstract M-1076).
Received: August 5, 2010
Accepted after revision: September 10, 2010
Published online: November 9, 2010
Number of Print Pages : 20
Number of Figures : 6, Number of Tables : 0, Number of References : 37
Journal of Innate Immunity
Vol. 3, No. 2, Year 2011 (Cover Date: February 2011)
Journal Editor: Herwald H. (Lund), Egesten A. (Lund)
ISSN: 1662-811X (Print), eISSN: 1662-8128 (Online)
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