IL-13 attenuates early local CXCL2-dependent neutrophil recruitment for Candida albicans clearance during a severe murine systemic infection
| Autor: | Yasunori Ogura, Ken Iseki, Kazuaki Arai, Natsuo Yamamoto, Yoshinobu Abe, Kiwamu Nakamura, Chiye Sakurai, Kiyotaka Hatsuzawa, Keiji Kanemitsu, Choichiro Tase |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Neutrophils Immunology Chemokine CXCL2 Kidney Microbiology Proinflammatory cytokine 03 medical and health sciences Interferon-gamma Mice 0302 clinical medicine Downregulation and upregulation Candida albicans Immunology and Allergy Medicine Animals Humans Cells Cultured Colony-forming unit Mice Knockout Mice Inbred BALB C Interleukin-13 biology business.industry Candidiasis Hematology biology.organism_classification Corpus albicans Up-Regulation CXCL2 Disease Models Animal 030104 developmental biology Neutrophil Infiltration Interleukin 13 Disease Progression business 030215 immunology Transforming growth factor |
| Zdroj: | Immunobiology. 224(1) |
| ISSN: | 1878-3279 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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