A Synergy Between Endotoxin and (1→3)-Beta-D-Glucan Enhanced Neutrophil Extracellular Traps in <i>Candida</i> Administered Dextran Sulfate Solution Induced Colitis in FcGRIIB-/- Lupus Mice, an Impact of Intestinal Fungi in Lupus.

Saithong, Supichcha, Saisorn, Wilasinee ORCID: 0000-0002-0074-0389, Visitchanakun, Peerapat, Sae-Khow, Kritsanawan, Chiewchengchol, Direkrit ORCID: 0000-0003-1824-7012 and Leelahavanichkul, Asada (2021) A Synergy Between Endotoxin and (1→3)-Beta-D-Glucan Enhanced Neutrophil Extracellular Traps in <i>Candida</i> Administered Dextran Sulfate Solution Induced Colitis in FcGRIIB-/- Lupus Mice, an Impact of Intestinal Fungi in Lupus. Journal of inflammation research, 14. pp. 2333-2352.

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Official URL: http://dx.doi.org/10.2147/jir.s305225

Abstract

<h4>Introduction</h4>The translocation of organismal molecules from gut into blood circulation might worsen the disease severity of lupus through the induction of neutrophil extracellular traps (NETs).<h4>Methods</h4>An impact of lipopolysaccharide (LPS) and (1→3)-β-D-glucan (BG), components of gut bacteria and fungi, respectively, on NETs formation, was explored in lupus models, Fc gamma receptor IIB deficiency (FcGRIIB-/-) and Pristane injection, using <i>Candida-</i>administered dextran sulfate solution induced colitis (<i>Candida</i>-DSS) model.<h4>Results</h4>Severity of <i>Candida</i>-DSS in FcGRIIB-/- mice was more prominent than wild-type (WT) and Pristane mice as indicated by (i) colonic NETs using immunofluorescence of Ly6G, myeloperoxidase (MPO) and neutrophil elastase (NE) together with expression of <i>PAD4</i> and <i>IL-1β</i>, (ii) colonic immunoglobulin (Ig) deposition (immunofluorescence), (iii) gut-leakage by FITC-dextran assay, endotoxemia and serum BG, (iv) systemic inflammation (neutrophilia, serum cytokines, serum dsDNA and anti-dsDNA) and (v) renal injury (proteinuria, glomerular NETs and Ig deposition).<h4>Discussion</h4>The formation of NETs in <i>Candida</i>-DSS mice was more severe than non-<i>Candida</i>-DSS mice and NETs in <i>Candida</i>-DSS were more profound in FcGRIIB-/- mice than Pristane mice. Prominent NETs in <i>Candida</i>-DSS FcGRIIB-/- mice might be due to the profound responses against LPS+BG in FcGRIIB-/- neutrophils compared with WT cells. These data implied an impact of the inhibitory FcGRIIB in NETs formation and an influence of gut fungi in lupus exacerbation. Hence, gut fungi in a DSS-induced gut-leakage lupus model enhanced colonic NETs that facilitated gut translocation of organismal molecules and synergistically exacerbated lupus activity.

Item Type:	Article
Uncontrolled Keywords:	Candida, FcGRIIB deficient mice, Pristane mice, gut-leakage, neutrophil extracellular traps, systemic lupus erythematosus
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	23 Dec 2021 16:25
Last Modified:	18 Jan 2023 21:18
DOI:	10.2147/jir.s305225
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3145989