Intratracheal Candida administration induced lung dysbiosis, activated neutrophils, and worsened lung hemorrhage in pristane-induced lupus mice

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 21, 2025

Because the innate immunity might and fungi in lungs enhance severity of lupus-induced diffuse alveolar hemorrhage (DAH), intraperitoneal pristane injection was performed C57BL6 mice with intratracheal administration by Candida albicans or phosphate buffer solution (PBS). Despite similar pristane-induced lupus (proteinuria, serum creatinine, anti-dsDNA) at 5 weeks model, worsened several characteristics, including mortality, body weight, cytokines (TNF-α IL-6), lung score, tissue (TNF-α, IL-6, IL-10), but not gut permeability (FITC-dextran assay), IL-10, immune cells spleens (flow cytometry analysis), activities peritoneal macrophages (polymerase-chain reaction). Although reduced proteobacterial abundance altered alpha beta diversity compared PBS control, microbiota different between pristane- non-pristane-administered mice. prominent Gram-negative bacteria role neutrophils DAH, lipopolysaccharide (LPS) without heat-killed preparation tested. Indeed, LPS induced more severe pro-inflammatory than stimulation alone as indicated expression genes IL-1β, Dectin-1, NF-κB). In conclusion, partly through enhanced neutrophil responses against fungi. More studies on colonization sputum from patients DAH are interesting.

Language: Английский

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Accelerating and protective effects toward cancer growth in cGAS and FcgRIIb deficient mice, respectively, an impact of macrophage polarization

Inflammation Research, Journal Year: 2025, Volume and Issue: 74(1)

Published: April 24, 2025

Language: Английский

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Alcohol-induced gut permeability defect through dysbiosis and enterocytic mitochondrial interference causing pro-inflammatory macrophages in a dose dependent manner

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 27, 2025

Although toxicity of alcohol toward the intestines and immunity is mentioned, there might be different effect in a low high dose rodent model development using simple SHIRPA binary score night useful. Hence, (6.30 1.26 g/kg/day) were administered for 16 weeks before determination several parameters. As such, peak blood concentration (BAC) approximately at 0.05 0.15%, respectively, 1 h post-administration, which correlated with 1.8 ± 0.8 7.2 0.6, respectively. After wk administration, significant liver injury high-dose was indicated by enzymes, weight, histology score, apoptosis, hepatic accumulation triglyceride (TG) oxidative stress (malondialdehyde; MDA) reduced anti-oxidant (glutathione). Meanwhile, low-dose demonstrated only elevated apoptosis increased TG MDA tissue. Leaky gut from both also FITC-dextran, endotoxemia, serum beta glucan, occludin. However, bacterial abundance (microbiome analysis) feces small bowel alcohol, but not dose, control (increased Alitipes spp. Lachnospiraceae). In conclusion, low- induced leaky gut, while caused dysbiosis damaged mitochondria enhanced glycolysis enterocytes macrophages. more sensitive than to determine alcohol-induced intestinal injury.

Language: Английский

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Beta-Glucan from S. cerevisiae Protected AOM-Induced Colon Cancer in cGAS-Deficient Mice Partly through Dectin-1-Manipulated Macrophage Cell Energy

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(18), P. 10951 - 10951

Published: Sept. 19, 2022

Although the impacts of

Language: Английский

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The Relationships between Intestinal Permeability and Target Antibodies for a Spectrum of Autoimmune Diseases

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(22), P. 16352 - 16352

Published: Nov. 15, 2023

The worldwide prevalence of autoimmune diseases that have limited treatment options and preventive strategies is rapidly rising. There growing evidence the microbiota integrity intestinal barrier play a role in diseases. potential to evaluate for susceptible individuals determine whether restoring junction impacts an important area research requires further attention. In permeability model diseases, breakdown tight proteins (zonulin/occludin) allows bacteria, toxins, undigested dietary proteins, other antigens pass into lumen, thereby increasing number inflammatory reactions activation immune cells throughout body. this study, we investigate relationship between zonulin/occludin antibodies, which are used permeability, with autoantibodies diagnose autoimmunity. Our investigation may identify significant levels circulating human subjects compared those without permeability. Furthermore, identified positive linear correlations serum occludin/zonulin antibodies could be

Language: Английский

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Enhanced lupus progression in alcohol‐administered Fc gamma receptor‐IIb–deficiency lupus mice, partly through leaky gut‐induced inflammation

Immunology and Cell Biology, Journal Year: 2023, Volume and Issue: 101(8), P. 746 - 765

Published: Aug. 14, 2023

Abstract Alcohol can induce a leaky gut, with translocation of microbial molecules from the gut into blood circulation. Although contribution inflammation to organ‐mediated damage in lupus has been previously demonstrated, mechanistic roles alcohol consumption activation are not known. Herein, we tested effects 10‐week lasting administration on organ damages and immune responses 8‐week‐old lupus‐prone Fc gamma receptor IIb–deficient (FcγRIIb −/− ) mice. Our study endpoints were evaluation systemic assessment fecal dysbiosis along endotoxemia. In comparison alcohol‐administered wild‐type mice, FcγRIIb mice demonstrated more prominent liver (enzyme, histological score, apoptosis, malondialdehyde oxidant) serum interleukin(IL)‐6 levels, despite similarity (fluorescein isothiocyanate–dextran assay, endotoxemia occludin‐1 immunofluorescence), (microbiome analysis) All developed lupus‐like characteristics (serum anti‐dsDNA, proteinuria, creatinine kidney injury score) spleen whereas control showed only subtle anti‐dsDNA. Both lipopolysaccharide (LPS) similarly impaired enterocyte integrity (transepithelial electrical resistance), LPS, but alcohol, upregulated IL‐8 gene Caco‐2 cells. macrophages, mildly activated supernatant cytokines (tumor necrosis factor‐α IL‐6), M1 polarization–associated genes ( IL‐1β iNOS ), LPS prominently induced both parameters (more macrophages than wild type). There was no synergy plus compared alone enterocytes macrophages. conclusion, might exacerbate activity partly through profound

Language: Английский

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Possible Role of Dysbiosis of the Gut Microbiome in SLE

Current Rheumatology Reports, Journal Year: 2023, Volume and Issue: 25(12), P. 247 - 258

Published: Sept. 22, 2023

Language: Английский

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Microbiota and Recurrent Pregnancy Loss (RPL); More than a Simple Connection

Microorganisms, Journal Year: 2024, Volume and Issue: 12(8), P. 1641 - 1641

Published: Aug. 10, 2024

Recurrent Pregnancy Loss (RPL) affects 1–2% of women, and its triggering factors are unclear. Several studies have shown that the vaginal, endometrial, gut microbiota may play a role in RPL. A decrease quantity Lactobacillus crispatus local has been associated with an increase (vaginal endometrial) inflammatory response immune cell activation leads to pregnancy loss. The be triggered by gram-negative bacteria, lipopolysaccharides (LPS), viral infections, mycosis, or atypia (tumor growth). Bacterial structures metabolites produced could involved modulation responsible for molecular mimicry. Gut metabolic products amount circulating pro-inflammatory lymphocytes, which, turn, will migrate into vaginal endometrial tissues. Local Th1 Th17 subpopulations Treg tolerogenic NK cells accountable modulate response, increasing success. Analyzing necessary characterize some RPL patients. Although oral supplementation probiotics not modify microbiota, it benefit transplantation vagina enhance required achieve normal pregnancy. effect hormone stimulation progesterone maintain early on adequately studied, more research is needed this area. Well-designed clinical trials ascertain

Language: Английский

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Extracellular traps in peripheral blood mononuclear cell fraction in childhood-onset systemic lupus erythematosus

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Oct. 5, 2024

Although the role of low-density granulocytes (LDGs), neutrophils in peripheral blood mononuclear cell (PBMC) fraction, and neutrophil extracellular traps (NETs) assessing lupus disease severity is acknowledged, data specific to childhood-onset remains scarce. This study analyzed 46 patients with systemic erythematosus (82.6% females, mean age 14.5 ± 0.3 years), including 26 cases normal complement levels 20 low levels, along healthy adult volunteers. Key parameters that distinguished volunteers from differentiated between were serum interferon (IFN)-α, citrullinated histone 3 (CitH3), (ETs) LDGs. However, NETs (assessed by nuclear staining morphology), LDG abundance, other (such as endotoxemia, cytokines, double-stranded (ds) DNA) did not show such differentiation. When lipopolysaccharide (LPS) was administered LDGs PBMC it induced ETs both groups, indicating inducible nature ETs. In volunteers, activation recombinant IFN-α or dsDNA isolated (identified using immunofluorescent for CitH3, myeloperoxidase, elastase) at 45 min h post-stimulation, respectively. Additionally, approximately half underwent late apoptosis determined flow cytometry analysis. Activation also led a more pronounced expression CD66b, an adhesion molecule, compared regular-density neutrophils, suggesting higher activity conclusion, and/or may transform into before progressing NETosis apoptosis, potentially exacerbating through death-induced self-antigens. Therefore, could provide deeper insights pathophysiology lupus.

Language: Английский

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Comparative time-series analyses of gut microbiome profiles in genetically and chemically induced lupus-prone mice and the impacts of fecal transplantation

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 2, 2024

Although the association between gut dysbiosis (imbalance of microbiota) in systemic lupus erythematosus (SLE) is well-known, simultaneous exploration fecal and different intestinal sections before after onset (at 2, 4, 6, 8, 10 months old) resulting from loss inhibitory Fc gamma receptor IIb (FcGIIb) pristane induction have never been conducted. Anti-dsDNA (an important autoantibody) proteinuria developed as early 6 old both models, with higher levels FcGRIIb deficient (FcGRIIb-/-) mice. Compared to healthy control at 2 4 months, mice (both FcGRRIIb-/- pristane) demonstrated an alteration indicated by Shannon alpha diversity index, highlighting influences lupus- age-induced dysbiosis, respectively. Non-metric multidimensional scaling (NMDS) revealed that microbiota FcGRIIb-/- were distinct age-matched all timepoints month, p < 0.05), while showed divergence only some timepoints. Analyses similarity among cecum, colon, feces, contrasting those small intestines (duodenum, jejunum, ileum). Subtle differences found feces assessed several analyses, for examples, similar or dissimilar distances (NMDS), neighbor-joining clustering, potential metabolisms (KEGG pathway analysis). Due (feces sections) control, rebalancing using rectal administration (fecal transplantation; FMT) 7-month-old FcGIIb-/- (the established lupus; positive anti-dsDNA proteinuria) was performed. In comparison without FMT, FMT (more effect on female than male mice) lower microbiome (16s DNA gene copy number) patterns control. conclusion, (FcGRIIb-/- diverged 4-6 old, correlating characteristics (anti-dsDNA proteinuria). The suggested a possible various molecular causes. Furthermore, appeared mitigate reduce anti-dsDNA, supporting benefit lupus, more studies are warranted.

Language: Английский

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