&lt;b&gt;&lt;i&gt;Candida&lt;/i&gt;&lt;/b&gt; Administration Worsens Neutrophil Extracellular Traps in Renal Ischemia Reperfusion Injury Mice: An Impact of Gut Fungi on Acute Kidney Injury

Saithong, Supichcha; Saisorn, Wilasinee; Dang, Cong Phi; Visitchanakun, Peerapat; Chiewchengchol, Direkrit; Leelahavanichkul, Asada

doi:10.1159/000521633

Cited by 13 publications

(10 citation statements)

References 89 publications

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“…Studies have reported that the activation of neutrophil surface receptors such as NOX, Toll-like receptors (TLRs), Fc gamma receptor (FcγR), macrophage-1 antigen (Mac-1), programmed death ligand 1 (PD-L1), S1PR2 and dectin-1 may be involved in the initiation of NETosis, which involves the release of ROS (both NOX-derived and mitochondria-derived) or the elevation of intracellular calcium concentrations ( 59 – 62 ) ( Figure 1 ). ROS-related upstream signaling pathways, including protein kinase C (PKC), Raf/MEK/ERK, P38 mitogen-activated protein kinase (MAPK), Src/Syk, and PI3k/Akt, may medicate the NETosis induced by PMA, immobilized immune complexes, microbes, and diphenyl phosphate (DPHP) ( 51 , 63 – 66 ).…”

Section: Mechanisms Underlying the Formation Of Neutrophil Extracellu...mentioning

confidence: 99%

“…Meanwhiles, in vitro , the activation of P2RX1 promoted platelet ATP release, which subsequently promoted the glycolytic metabolism of neutrophils and NET formation ( 105 ). In addition, the oral administration of Candida albicans to mice prior to renal I/R increased systemic inflammation and NETs through the activation of TLR-4 and dectin-1, exacerbating renal IRI ( 62 ). In line with these findings, Complement C3 KO mice with renal I/R showed attenuated renal injury when neutrophil infiltration and NET formation were reduced ( 106 ).…”

Section: Extracellular Traps In Organ Ischemia Reperfusion Injurymentioning

confidence: 99%

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The role of extracellular traps in ischemia reperfusion injury

Zhang

et al. 2022

Front. Immunol.

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In response to strong signals, several types of immune cells release extracellular traps (ETs), which are web-like structures consisting of DNA decorated with various protein substances. This process is most commonly observed in neutrophils. Over the past two decades, ET formation has been recognized as a unique mechanism of host defense and pathogen destruction. However, the role of ETs in sterile inflammation has only been studied extensively in recent years. Ischemia reperfusion injury (IRI) is a type of sterile inflammatory injury. Several studies have reported that ETs have an important role in IRI in various organs. In this review, we describe the release of ETs by various types of immune cells and focus on the mechanism underlying the formation of neutrophil ETs (NETs). In addition, we summarize the role of ETs in IRI in different organs and their effects on tumors. Finally, we discuss the value of ETs as a potential therapeutic target for organ IRI and present possible challenges in conducting studies on IRI-related ETs as well as future research directions and prospects.

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Section: Mechanisms Underlying the Formation Of Neutrophil Extracellu...mentioning

confidence: 99%

Section: Extracellular Traps In Organ Ischemia Reperfusion Injurymentioning

confidence: 99%

The role of extracellular traps in ischemia reperfusion injury

Zhang

et al. 2022

Front. Immunol.

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“…The synergy or additive effect of BG presentation upon LPS responses is intensively demonstrated through the activation of several innate immune cells (neutrophils, macrophages, and dendritic cells) [5,17,30,[54][55][56][57][58][59][60][61], possibly with the crosslink between TLR-4 and Dectin-1, the pattern recognition receptors (PRRs) for LPS and BG, respectively [62]. The similar downstream signaling through the NF-κB transcription factor of TLR-4 and Dectin-1 in these immune cells may be another explanation of the LPS-BG additive impact on several organs through the activation of immune cells (especially macrophages) inside these organs.…”

Section: The Additive Inflammatory Effect Of Lps Plus Bg a Key Pro-in...mentioning

confidence: 99%

Candida Administration in 5/6 Nephrectomized Mice Enhanced Fibrosis in Internal Organs: An Impact of Lipopolysaccharide and (1→3)-β-D-Glucan from Leaky Gut

Tungsanga

Udompornpitak

Worasilchai

et al. 2022

IJMS

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Uremic toxins and gut dysbiosis in advanced chronic kidney disease (CKD) can induce gut leakage, causing the translocation of gut microbial molecules into the systemic circulation. Lipopolysaccharide (LPS) and (1→3)-β-D-glucan (BG) are the major gut microbial molecules of Gram-negative bacteria and fungi, respectively, and can induce inflammation in several organs. Here, the fibrosis in the kidney, liver, and heart was investigated in oral C. albicans-administered 5/6 nephrectomized (Candida-5/6 Nx) mice. At 20 weeks post 5/6 Nx, Candida-5/6 Nx mice demonstrated increased 24 h proteinuria, liver enzymes, and serum cytokines (TNF-α, IL-6, and IL-10), but not weight loss, systolic blood pressure, hematocrit, serum creatinine, or gut-derived uremic toxins (TMAO and indoxyl sulfate), compared to in 5/6 Nx alone. The gut leakage in Candida-5/6 Nx was more severe, as indicated by FITC-dextran assay, endotoxemia, and serum BG. The areas of fibrosis from histopathology, along with the upregulated gene expression of Toll-like receptor 4 (TLR-4) and Dectin-1, the receptors for LPS and BG, respectively, were higher in the kidney, liver, and heart. In vitro, LPS combined with BG increased the supernatant IL-6 and TNF-α, upregulated the genes of pro-inflammation and pro-fibrotic processes, Dectin-1, and TLR-4 in renal tubular (HK-2) cells and hepatocytes (HepG2), when compared with LPS or BG alone. This supported the pro-inflammation-induced fibrosis and the possible LPS–BG additive effects on kidney and liver fibrosis. In conclusion, uremia-induced leaky gut causes the translocation of gut LPS and BG into circulation, which activates the pro-inflammatory and pro-fibrotic pathways, causing internal organ fibrosis. Our results support the crosstalk among several organs in CKD through a leaky gut.

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“…Then, fungi in the gut can alter bacterial compositions in the gut and contribute to leaky gut-induced systemic inflammation in uremia through glucanemia and endotoxemia ( 22 ) and the abundance of gut organisms might be correlated with the level of pathogen molecules in blood during uremia-induced leaky gut ( 23 ). Due to the difference in the abundance of fungi in rodents versus humans, Candida administration might make the models more resemble humans ( 19 , 24 – 26 ). Indeed, the abundance of Candida spp.…”

Section: Introductionmentioning

confidence: 99%

Lacticaseibacilli attenuated fecal dysbiosis and metabolome changes in Candida-administered bilateral nephrectomy mice

Chancharoenthana

Kamolratanakul²,

Visitchanakun³

et al. 2023

Front. Immunol.

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The impacts of metabolomic changes (reduced short-chain-fatty acids; SCFAs) in uremic condition is not fully understood. Once daily Candida gavage with or without probiotics (different times of administration) for 1 week prior to bilateral nephrectomy (Bil Nep) in 8-week-old C57BL6 mice as the possible models more resemble human conditions were performed. Candida-administered Bil Nep mice demonstrated more severe conditions than Bil Nep alone as indicated by mortality (n = 10/group) and other 48 h parameters (n = 6-8/group), including serum cytokines, leaky gut (FITC-dextran assay, endotoxemia, serum beta-glucan, and loss of Zona-occludens-1), and dysbiosis (increased Enterobacteriaceae with decreased diversity in microbiome analysis) (n = 3/group for fecal microbiome) without the difference in uremia (serum creatinine). With nuclear magnetic resonance metabolome analysis (n = 3-5/group), Bil Nep reduced fecal butyric (and propionic) acid and blood 3-hydroxy butyrate compared with sham and Candida-Bil Nep altered metabolomic patterns compared with Bil Nep alone. Then, Lacticaseibacillus rhamnosus dfa1 (SCFA-producing Lacticaseibacilli) (n = 8/group) attenuated the model severity (mortality, leaky gut, serum cytokines, and increased fecal butyrate) of Bil Nep mice (n = 6/group) (regardless of Candida). In enterocytes (Caco-2 cells), butyrate attenuated injury induced by indoxyl sulfate (a gut-derived uremic toxin) as indicated by transepithelial electrical resistance, supernatant IL-8, NFκB expression, and cell energy status (mitochondria and glycolysis activities by extracellular flux analysis). In conclusion, the reduced butyrate by uremia was not enhanced by Candida administration; however, the presence of Candida in the gut induced a leaky gut that was attenuated by SCFA-producing probiotics. Our data support the use of probiotics in uremia.

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<b><i>Candida</i></b> Administration Worsens Neutrophil Extracellular Traps in Renal Ischemia Reperfusion Injury Mice: An Impact of Gut Fungi on Acute Kidney Injury

Cited by 13 publications

References 89 publications

The role of extracellular traps in ischemia reperfusion injury

The role of extracellular traps in ischemia reperfusion injury

Candida Administration in 5/6 Nephrectomized Mice Enhanced Fibrosis in Internal Organs: An Impact of Lipopolysaccharide and (1→3)-β-D-Glucan from Leaky Gut

Lacticaseibacilli attenuated fecal dysbiosis and metabolome changes in Candida-administered bilateral nephrectomy mice

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