IL-13 attenuates early local CXCL2-dependent neutrophil recruitment for Candida albicans clearance during a severe murine systemic infection

Yoshinobu Abe; Natsuo Yamamoto; Kiwamu Nakamura; Kazuaki Arai; Chiye Sakurai; Kiyotaka Hatsuzawa; Yasunori Ogura; Ken Iseki; Choichiro Tase; Keiji Kanemitsu

doi:10.1016/j.imbio.2018.11.002

IL-13 attenuates early local CXCL2-dependent neutrophil recruitment for Candida albicans clearance during a severe murine systemic infection

Immunobiology. 2019 Jan;224(1):15-29. doi: 10.1016/j.imbio.2018.11.002. Epub 2018 Nov 24.

Authors

Affiliations

¹ Department of Emergency and Critical Care Medicine, Fukushima Medical University, Hikarigaoka, Fukushima, 960-1295, Japan.
² Department of Infection Control, Fukushima Medical University, Hikarigaoka, Fukushima, 960-1295, Japan; Health and Welfare Center of Sendai City, Taihaku Ward Branch Office, Taihaku-ku, Nagamachi-minami 1-15, Sendai, 982-8601, Japan. Electronic address: n-yama@fmu.ac.jp.
³ Department of Infection Control, Fukushima Medical University, Hikarigaoka, Fukushima, 960-1295, Japan.
⁴ Division of Molecular Biology, School of Life Sciences, Faculty of Medicine, Tottori University, Yonago, Tottori, 683-8503, Japan.
⁵ Division of Human Life and Environmental Sciences, Nara Women's University, Kita-Uoya Nishimachi, Nara, 630-8506, Japan.

PMID: 30514570
DOI: 10.1016/j.imbio.2018.11.002

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.

Keywords: Blood stream infection; CXCL2; Candida albicans; Interleukin-13; Polymorphonuclear neutrophil; TGF-β.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Candida albicans / physiology*
Candidiasis / immunology*
Cells, Cultured
Chemokine CXCL2 / genetics
Chemokine CXCL2 / metabolism
Disease Models, Animal
Disease Progression
Humans
Interferon-gamma / metabolism
Interleukin-13 / genetics
Interleukin-13 / metabolism*
Kidney / immunology*
Kidney / microbiology
Mice
Mice, Inbred BALB C
Mice, Knockout
Neutrophil Infiltration
Neutrophils / immunology*
Up-Regulation

Substances

Chemokine CXCL2
Interleukin-13
Interferon-gamma