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

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.

journal_name

Immunobiology

journal_title

Immunobiology

authors

Abe Y,Yamamoto N,Nakamura K,Arai K,Sakurai C,Hatsuzawa K,Ogura Y,Iseki K,Tase C,Kanemitsu K

doi

10.1016/j.imbio.2018.11.002

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

15-29

issue

1

eissn

0171-2985

issn

1878-3279

pii

S0171-2985(18)30190-6

journal_volume

224

pub_type

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