1. IL-13 attenuates early local CXCL2-dependent neutrophil recruitment for Candida albicans clearance during a severe murine systemic infection.
- Author
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Abe Y, Yamamoto N, Nakamura K, Arai K, Sakurai C, Hatsuzawa K, Ogura Y, Iseki K, Tase C, and Kanemitsu K
- Subjects
- Animals, Cells, Cultured, Chemokine CXCL2 genetics, Chemokine CXCL2 metabolism, Disease Models, Animal, Disease Progression, Humans, Interferon-gamma metabolism, Interleukin-13 genetics, Kidney microbiology, Mice, Mice, Inbred BALB C, Mice, Knockout, Neutrophil Infiltration, Up-Regulation, Candida albicans physiology, Candidiasis immunology, Interleukin-13 metabolism, Kidney immunology, Neutrophils immunology
- Abstract
To investigate the role of IL-13 during a severe systemic Candida albicans infection, BALB/c control and IL-13
-/- mice were examined for colony forming units (CFU) in the kidneys and survival days after intravenous infection. Proinflammatory mediators and cell recruitment into the tissue were measured by quantitative real-time PCR, a multiple ELISA system, and morphological cell differentiation. The IL-13-/- group exhibited a lower CFU number in the kidneys at 4 days and survived longer than the control mice, which was accompanied by significantly higher expression of C-X-C motif ligand 2 (CXCL2), IFN-γ, and polymorphonuclear neutrophils (PMNs) in the infected kidneys. By contrast, the expression of transforming growth factor β (TGF-β) and IL-17 A on day 10 were significantly higher in the control mice than in the IL-13-/- group. When using an intratracheal infection model, the IL-13-/- group recruited a greater number of PMNs in 6 h, with rapidly increased CXCL2 in the alveolar space. In vitro testing with cultured bone-marrow-derived cells demonstrated rapid CXCL2 mRNA upregulation at 3 h after contact with C. albicans, which decreased with recombinant IL-13 pretreatment, whereas rIL-13 retained TGF-β upregulation. In a murine model of Candida systemic infection, preexistent IL-13 limits both the rapid CXCL2 elevation and PMN aggregation in the target organ to suppress inflammatory mediators, which also attenuates local pathogen clearance within four days., (Copyright © 2018 Elsevier GmbH. All rights reserved.)- Published
- 2019
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