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,1– 3 Wilasinee Saisorn,3 Peerapat Visitchanakun,3 Kritsanawan Sae-khow,3 Direkrit Chiewchengchol,2,3 Asada Leelahavanichkul2,3 1Medical Microbiology, Interdisciplinary and International Program, Graduate School, Chulalongkorn University, Bangkok, Thailand; 2Immunology Un...
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2021
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oai:doaj.org-article:0188c05bbf194e249c78d264ae7bcae22021-12-02T15:50:41ZA 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 Lupus1178-7031https://doaj.org/article/0188c05bbf194e249c78d264ae7bcae22021-06-01T00:00:00Zhttps://www.dovepress.com/a-synergy-between-endotoxin-and-13-beta-d-glucan-enhanced-neutrophil-e-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Supichcha Saithong,1– 3 Wilasinee Saisorn,3 Peerapat Visitchanakun,3 Kritsanawan Sae-khow,3 Direkrit Chiewchengchol,2,3 Asada Leelahavanichkul2,3 1Medical Microbiology, Interdisciplinary and International Program, Graduate School, Chulalongkorn University, Bangkok, Thailand; 2Immunology Unit, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 3Translational Research in Inflammation and Immunology Research Unit (TRIRU), Department of Microbiology, Chulalongkorn University, Bangkok, ThailandCorrespondence: Asada Leelahavanichkul; Direkrit ChiewchengcholImmunology Unit, Department of Microbiology, Chulalongkorn University, Bangkok, 10330, ThailandTel +66-2-256-4251Fax +66-2-252-6920Email aleelahavanit@gmail.com; cdirekrit@live.comIntroduction: 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: FcGRIIB deficient mice, Pristane mice, systemic lupus erythematosus, neutrophil extracellular traps, Candida, gut-leakageSaithong SSaisorn WVisitchanakun PSae-khow KChiewchengchol DLeelahavanichkul ADove Medical Pressarticlefcgriib deficient micepristane micesystemic lupus erythematosusneutrophil extracellular trapscandidagut-leakagePathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 2333-2352 (2021) |
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DOAJ |
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DOAJ |
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EN |
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fcgriib deficient mice pristane mice systemic lupus erythematosus neutrophil extracellular traps candida gut-leakage Pathology RB1-214 Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
fcgriib deficient mice pristane mice systemic lupus erythematosus neutrophil extracellular traps candida gut-leakage Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Saithong S Saisorn W Visitchanakun P Sae-khow K Chiewchengchol D Leelahavanichkul A 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 |
| description |
Supichcha Saithong,1– 3 Wilasinee Saisorn,3 Peerapat Visitchanakun,3 Kritsanawan Sae-khow,3 Direkrit Chiewchengchol,2,3 Asada Leelahavanichkul2,3 1Medical Microbiology, Interdisciplinary and International Program, Graduate School, Chulalongkorn University, Bangkok, Thailand; 2Immunology Unit, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 3Translational Research in Inflammation and Immunology Research Unit (TRIRU), Department of Microbiology, Chulalongkorn University, Bangkok, ThailandCorrespondence: Asada Leelahavanichkul; Direkrit ChiewchengcholImmunology Unit, Department of Microbiology, Chulalongkorn University, Bangkok, 10330, ThailandTel +66-2-256-4251Fax +66-2-252-6920Email aleelahavanit@gmail.com; cdirekrit@live.comIntroduction: 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: FcGRIIB deficient mice, Pristane mice, systemic lupus erythematosus, neutrophil extracellular traps, Candida, gut-leakage |
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article |
| author |
Saithong S Saisorn W Visitchanakun P Sae-khow K Chiewchengchol D Leelahavanichkul A |
| author_facet |
Saithong S Saisorn W Visitchanakun P Sae-khow K Chiewchengchol D Leelahavanichkul A |
| author_sort |
Saithong S |
| title |
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 |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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 |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/0188c05bbf194e249c78d264ae7bcae2 |
| work_keys_str_mv |
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