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

Supichcha Saithong; Wilasinee Saisorn; Peerapat Visitchanakun; Kritsanawan Sae-Khow; Direkrit Chiewchengchol; Asada Leelahavanichkul

doi:10.2147/JIR.S305225

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

J Inflamm Res. 2021 Jun 1:14:2333-2352. doi: 10.2147/JIR.S305225. eCollection 2021.

Authors

Supichcha Saithong^{1

2

3}, Wilasinee Saisorn³, Peerapat Visitchanakun³, Kritsanawan Sae-Khow³, Direkrit Chiewchengchol^{2

3}, Asada Leelahavanichkul^{2

3}

Affiliations

¹ Medical Microbiology, Interdisciplinary and International Program, Graduate School, Chulalongkorn University, Bangkok, Thailand.
² Immunology Unit, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
³ Translational Research in Inflammation and Immunology Research Unit (TRIRU), Department of Microbiology, Chulalongkorn University, Bangkok, Thailand.

Abstract

Introduction: 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).

Methods: 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 Candida-administered dextran sulfate solution induced colitis (Candida-DSS) model.

Results: Severity of Candida-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 PAD4 and IL-1β, (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).

Discussion: The formation of NETs in Candida-DSS mice was more severe than non-Candida-DSS mice and NETs in Candida-DSS were more profound in FcGRIIB-/- mice than Pristane mice. Prominent NETs in Candida-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.

Keywords: Candida; FcGRIIB deficient mice; Pristane mice; gut-leakage; neutrophil extracellular traps; systemic lupus erythematosus.