scholarly journals Clustering of Tir during enteropathogenic E. coli infection triggers calcium influx–dependent pyroptosis in intestinal epithelial cells

PLoS Biology ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. e3000986
Author(s):  
Qiyun Zhong ◽  
Theodoros I. Roumeliotis ◽  
Zuza Kozik ◽  
Massiel Cepeda-Molero ◽  
Luis Ángel Fernández ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Type Iii Secretion ◽  
Calcium Influx ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Independent Manner ◽  
E Coli ◽  
T3ss Effector

Clustering of the enteropathogenic Escherichia coli (EPEC) type III secretion system (T3SS) effector translocated intimin receptor (Tir) by intimin leads to actin polymerisation and pyroptotic cell death in macrophages. The effect of Tir clustering on the viability of EPEC-infected intestinal epithelial cells (IECs) is unknown. We show that EPEC induces pyroptosis in IECs in a Tir-dependent but actin polymerisation-independent manner, which was enhanced by priming with interferon gamma (IFNγ). Mechanistically, Tir clustering triggers rapid Ca2+ influx, which induces lipopolysaccharide (LPS) internalisation, followed by activation of caspase-4 and pyroptosis. Knockdown of caspase-4 or gasdermin D (GSDMD), translocation of NleF, which blocks caspase-4 or chelation of extracellular Ca2+, inhibited EPEC-induced cell death. IEC lines with low endogenous abundance of GSDMD were resistant to Tir-induced cell death. Conversely, ATP-induced extracellular Ca2+ influx enhanced cell death, which confirmed the key regulatory role of Ca2+ in EPEC-induced pyroptosis. We reveal a novel mechanism through which infection with an extracellular pathogen leads to pyroptosis in IECs.

scholarly journals Positive regulation of Type III secretion effectors and virulence by RyhB paralogs in Salmonella enterica serovar Enteritidis

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Binjie Chen ◽  
Xianchen Meng ◽  
Jie Ni ◽  
Mengping He ◽  
Yanfei Chen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Type Iii Secretion ◽  
Salmonella Enterica ◽  
Intestinal Epithelial Cells ◽  
Type Iii Secretion System ◽  
Secretion System ◽  
Intestinal Epithelial ◽  
Type Iii ◽  
Effector Gene ◽  
T3ss Effector

AbstractSmall non-coding RNA RyhB is a key regulator of iron homeostasis in bacteria by sensing iron availability in the environment. Although RyhB is known to influence bacterial virulence by interacting with iron metabolism related regulators, its interaction with virulence genes, especially the Type III secretion system (T3SS), has not been reported. Here, we demonstrate that two RyhB paralogs of Salmonella enterica serovar Enteritidis upregulate Type III secretion system (T3SS) effectors, and consequently affect Salmonella invasion into intestinal epithelial cells. Specifically, we found that RyhB-1 modulate Salmonella response to stress condition of iron deficiency and hypoxia, and stress in simulated intestinal environment (SIE). Under SIE culture conditions, both RyhB-1 and RyhB-2 are drastically induced and directly upregulate the expression of T3SS effector gene sipA by interacting with its 5′ untranslated region (5′ UTR) via an incomplete base-pairing mechanism. In addition, the RyhB paralogs upregulate the expression of T3SS effector gene sopE. By regulating the invasion-related genes, RyhBs in turn affect the ability of S. Enteritidis to adhere to and invade into intestinal epithelial cells. Our findings provide evidence that RyhBs function as critical virulence factors by directly regulating virulence-related gene expression. Thus, inhibition of RyhBs may be a potential strategy to attenuate Salmonella.

Balance of bacterial pro- and anti-inflammatory mediators dictates net effect of enteropathogenicEscherichia colion intestinal epithelial cells

2006 ◽  
Vol 290 (4) ◽  
pp. G685-G694 ◽  
Author(s):  
Rachna Sharma ◽  
Samuel Tesfay ◽  
Farol L. Tomson ◽  
Rajani P. Kanteti ◽  
V. K. Viswanathan ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Host Cells ◽  
Intestinal Epithelial ◽  
E Coli ◽  
Inflammatory Proteins ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Prior Infection

Enteropathogenic Escherichia coli (EPEC) virulence requires a type III secretion system (TTSS) to deliver effector molecules in host cells. Although the TTSS is crucial to EPEC pathogenesis, its function in EPEC-induced inflammation is not known. The aim of this study was to investigate the role of the TTSS in EPEC-induced inflammation. HT-29 intestinal epithelial cells were infected with wild-type (WT) EPEC or select mutant strains or exposed to corresponding filter-sterilized supernatants (SN), and interleukin-8 (IL-8) secretion was determined by ELISA. EPEC SN stimulated significantly greater IL-8 production than EPEC organisms. Flagellin, as well as a TTSS-independent >50-kDa nonflagellin protein, was found to significantly contribute to this response. Dose-response studies showed that increasing concentrations of WT SN proportionally increased IL-8, whereas increasing multiplicity of infection of EPEC inversely correlated with IL-8 secretion, suggesting that EPEC dampens this host response. Infection with Δ escN (nonfunctional TTSS) markedly increased IL-8 compared with WT, indicating that a functional TTSS is required for this anti-inflammatory property; complementation of escN restored the attenuated response. Mutation of espB also enhanced the IL-8 response, and complementation returned IL-8 to near WT levels, suggesting involvement of this effector. The anti-inflammatory effect extends to both bacterial and host-derived proinflammatory stimuli, since prior infection with EPEC suppressed the IL-8 response to tumor necrosis factor-α, IL-1β, and enterohemorrhagic E. coli flagellin. These findings indicate that EPEC-induced inflammation is a balance between pro- and anti-inflammatory proteins; extracellular factors, including flagellin and an unidentified TTSS-independent, >50-kDa protein, trigger inflammation while intracellular TTSS-dependent factors, including EspB, attenuate this response.

Prevention of Dextran Sulfate Sodium-induced Mouse Colitis by a Fungal Protein Ling Zhi-8 via Promoting the Barrier Function of Intestinal Epithelial Cells

2021 ◽  
Author(s):  
Yu-Huan Chen ◽  
Jenn-Yeu Shin ◽  
Hsiu-Mei Wei ◽  
Chi-Chen Lin ◽  
Linda Chia-Hui Yu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Immune Cells ◽  
Ganoderma Lucidum ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Fungal Protein ◽  
Fungal Immunomodulatory Protein

A fungal immunomodulatory protein Ling Zhi-8 (LZ-8) isolated from Ganoderma lucidum (GL) regulates immune cells and inhibits tumor growth; however, the role of LZ-8 in intestinal epithelial cells (IECs) is...

scholarly journals Rspo3 regulates the abnormal differentiation of small intestinal epithelial cells in diabetic state

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ti-Dong Shan ◽  
Han Yue ◽  
Xue-Guo Sun ◽  
Yue-Ping Jiang ◽  
Li Chen
Keyword(s):  
Epithelial Cells ◽  
Bioinformatics Analysis ◽  
Intestinal Epithelial Cells ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Intestinal Epithelial ◽  
Epithelial Stem Cells ◽  
Diabetic State ◽  
Definitive Evidence

Abstract Background The complications caused by diabetes mellitus (DM) are the focus of clinical treatment. However, little is known about diabetic enteropathy (DE) and its potential underlying mechanism. Methods Intestinal epithelial cells (IECs) and intestinal epithelial stem cells (IESCs) were harvested from BKS.Cg-Dock7m+/+Leprdb/JNju (DM) mice, and the expression of R-Spondin 3 (Rspo3) was detected by RT-qPCR, Western blotting, immunohistochemistry, and immunofluorescence. The role of Rspo3 in the abnormal differentiation of IECs during DM was confirmed by knockdown experiments. Through miRNA expression profiling, bioinformatics analysis, and RT-qPCR, we further analyzed the differentiation-related miRNAs in the IECs from mice with DM. Results Abnormal differentiation of IECs was observed in the mice with DM. The expression of Rspo3 was upregulated in the IECs from the mice with DM. This phenomenon was associated with Rspo3 overexpression. Additionally, Rspo3 is a major determinant of Lgr5+ stem cell identity in the diabetic state. Microarray analysis, bioinformatics analysis, and luciferase reporter assays revealed that microRNA (miR)-380-5p directly targeted Rspo3. Moreover, miR-380-5p upregulation was observed to attenuate the abnormal differentiation of IECs by regulating Rspo3 expression. Conclusions Together, our results provide definitive evidence of the essential role of Rspo3 in the differentiation of IECs in DM.

scholarly journals Protective role of berberine on ulcerative colitis through modulating enteric glial cells–intestinal epithelial cells–immune cells interactions

2020 ◽  
Vol 10 (3) ◽  
pp. 447-461 ◽  
Author(s):  
Heng Li ◽  
Chen Fan ◽  
Huimin Lu ◽  
Chunlan Feng ◽  
Peilan He ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Epithelial Cells ◽  
Glial Cells ◽  
Immune Cells ◽  
Intestinal Epithelial Cells ◽  
Protective Role ◽  
Intestinal Epithelial ◽  
Enteric Glial Cells

Cholera Toxin Destabilizes Retromer to Inhibit NA + /H + Exchanger3 Activity in Intestinal Epithelial Cells- Possible Therapeutic Role of a Retromer Stabilizer in Treating Diarrhea

2017 ◽  
Vol 152 (5) ◽  
pp. S67
Author(s):  
Varsha Singh ◽  
Jianbo Yang ◽  
Jianyi Yin ◽  
Ming Tse ◽  
Nicholas C. Zachos ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cholera Toxin ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Therapeutic Role

Role of chemokine receptors and intestinal epithelial cells in the mucosal inflammation and tolerance

2016 ◽  
Vol 101 (2) ◽  
pp. 377-394 ◽  
Author(s):  
Neeraja Kulkarni ◽  
Manisha Pathak ◽  
Girdhari Lal
Keyword(s):  
Epithelial Cells ◽  
Chemokine Receptors ◽  
Intestinal Epithelial Cells ◽  
Mucosal Inflammation ◽  
Intestinal Epithelial

scholarly journals Expression of lysophosphatidic acid receptor 5 is necessary for the regulation of intestinal Na+/H+ exchanger 3 by lysophosphatidic acid in vivo

2018 ◽  
Vol 315 (4) ◽  
pp. G433-G442 ◽  
Author(s):  
Kayte A. Jenkin ◽  
Peijian He ◽  
C. Chris Yun
Keyword(s):  
Epithelial Cells ◽  
Lysophosphatidic Acid ◽  
Direct Evidence ◽  
Intestinal Epithelial Cells ◽  
Regulatory Role ◽  
Intestinal Epithelial ◽  
Fluid Absorption ◽  
Wild Type

Lysophosphatidic acid (LPA) is a bioactive lipid molecule, which regulates a broad range of pathophysiological processes. Recent studies have demonstrated that LPA modulates electrolyte flux in the intestine, and its potential as an antidiarrheal agent has been suggested. Of six LPA receptors, LPA5 is highly expressed in the intestine. Recent studies by our group have demonstrated activation of Na+/H+ exchanger 3 (NHE3) by LPA5. However, much of what has been elucidated was achieved using colonic cell lines that were transfected to express LPA5. In the current study, we engineered a mouse that lacks LPA5 in intestinal epithelial cells, Lpar5ΔIEC, and investigated the role of LPA5 in NHE3 regulation and fluid absorption in vivo. The intestine of Lpar5ΔIEC mice appeared morphologically normal, and the stool frequency and fecal water content were unchanged compared with wild-type mice. Basal rates of NHE3 activity and fluid absorption and total NHE3 expression were not changed in Lpar5ΔIEC mice. However, LPA did not activate NHE3 activity or fluid absorption in Lpar5ΔIEC mice, providing direct evidence for the regulatory role of LPA5. NHE3 activation involves trafficking of NHE3 from the terminal web to microvilli, and this mobilization of NHE3 by LPA was abolished in Lpar5ΔIEC mice. Dysregulation of NHE3 was specific to LPA, and insulin and cholera toxin were able to stimulate and inhibit NHE3, respectively, in both wild-type and Lpar5ΔIEC mice. The current study for the first time demonstrates the necessity of LPA5 in LPA-mediated stimulation of NHE3 in vivo. NEW & NOTEWORTHY This study is the first to assess the role of LPA5 in NHE3 regulation and fluid absorption in vivo using a mouse that lacks LPA5 in intestinal epithelial cells, Lpar5ΔIEC. Basal rates of NHE3 activity and fluid absorption, and total NHE3 expression were not changed in Lpar5ΔIEC mice. However, LPA did not activate NHE3 activity or fluid absorption in Lpar5ΔIEC mice, providing direct evidence for the regulatory role of LPA5.

Activation of NF-?B in intestinal epithelial cells by E. coli strains isolated from the colonic mucosa of IBD patients

2004 ◽  
Vol 19 (4) ◽  
pp. 334-342 ◽  
Author(s):  
Stefan Schreiber ◽  
Katia La Ferla ◽  
Dirk Seegert
Keyword(s):  
Epithelial Cells ◽  
Colonic Mucosa ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
E Coli
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