Compromised autophagy byMIR30Bbenefits the intracellular survival ofHelicobacter pylori

Tang, Bin; Li, Na; Gu, Jiang; Zhuang, Yuanyuan; Li, Qian; Wang, Haiguang; Fang, Yuqiang; B, Yu; Zhang, Jinyu; Xie, Qiang; Chen, Li; Jiang, Xuejun; Xiao, Bin; Zou, Quanming; Mao, Xuhu

doi:10.4161/auto.20159

Cited by 123 publications

(120 citation statements)

References 41 publications

Supporting

Mentioning

114

Contrasting

Order By: Relevance

“…More specifically, s1 VacA binds to the low-density lipoprotein receptor-related protein-1 triggering reactive oxygen speciesinduced autophagy (68). Compromised autophagy has been associated with increased capacity of H. pylori to survive in the intracellular environment (69). Interestingly, while both strains induced systemic Th1 responses and caused an expansion in the cytotoxic cell compartments, we found differences in their ability to persist in the stomach mucosa.…”

Section: Differentiation Of Naive Cd4mentioning

confidence: 37%

Helicobacter pylori Infection in a Pig Model Is Dominated by Th1 and Cytotoxic CD8⁺T Cell Responses

et al. 2013

View full text Add to dashboard Cite

Helicobacter pylori is the dominant member of the gastric microbiota and colonizes the stomach of more than 50% of the human population worldwide (1). H. pylori colonization usually does not cause illness, since 85% of infected people remain asymptomatic throughout life, but infection with strains bearing the cag (cytotoxin-associated gene) pathogenicity island can result in peptic ulcer disease, gastric lymphoma, and gastric adenocarcinoma, the second leading cause of cancer-related deaths, in 15% of infected individuals (2, 3). Conversely, there also is increasing evidence of H. pylori providing protection against esophageal and cardial pathologies (4-7), childhood asthma (8-10), childhood allergies (9, 11), and diabetes and obesity (12). This Gram-negative microaerophilic bacterium of the Epsilonproteobacteria has coevolved with humans for at least 50,000 years, indicating high adaptation capacity to the environmental niche of the human gastric mucosa and suggesting the ability to evade the immune system (13) through mechanisms that are incompletely understood. Infection with H. pylori in humans is associated mainly with a mucosal Th1 response, which is unsuccessful in clearing the bacteria from the stomach and can lead to more severe immunopathology (14). The pathogenicity of H. pylori is determined by various hostand pathogen-related factors, including the host's genetic background, age, and immune status and the bacterium's ability for antigenic variation, molecular mimicry, intracellular persistence, and expression of pathogenicity factors (15).Regulatory T (Treg) cells play a crucial role in H. pylori's ability to evade the immune system and persist in the gastric mucosa. Specifically, H. pylori can trigger a reprogramming of dendritic cells (DC) by downregulating major histocompatibility complex II (MHC-II) and inducing interleukin-10 (IL-10) and inhibiting IL-12 secretion, thereby inducing H. pylori-specific Treg cells (16)(17)(18). B cells also play a regulatory role by promoting IL-10 production in cocultured CD4 ϩ cells and subsequent conversion into a T T lymphocytes were found in the gastric epithelium and lamina propria (LP) of H. pylori-infected children with grade I to III gastritis (22, 23). Furthermore, the CD8 ϩ HLA-DR ϩ chronically activated memory T cell subset was expanded in peripheral blood of H. pylori-colonized children with duodenal ulcers (24), suggesting a role for CD8 ϩ T cells in H. pylori-mediated pathology. The majority of in vivo studies on the host responses to H. pylori are based on mouse models; however, in contrast to human

show abstract

Section: Differentiation Of Naive Cd4mentioning

confidence: 37%

Helicobacter pylori Infection in a Pig Model Is Dominated by Th1 and Cytotoxic CD8⁺T Cell Responses

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Then, the cells were trypsinized and analyzed using a FACScan flow cytometer and CellQuest software, as previously published. 39 Statistical analyses were performed as described above. Monodansylcadaverine staining MDC staining was used to quantify the induction of autophagy in Caco-2 cells.…”

Section: Acridine Orange Stainingmentioning

confidence: 99%

Shiga toxins induce autophagic cell death in intestinal epithelial cells via the endoplasmic reticulum stress pathway

Tang¹,

Li²,

Zhao³

et al. 2015

Autophagy

Self Cite

View full text Add to dashboard Cite

Keywords: autophagic cell death, autophagy, E. coli O157:H7, ER stress, Shiga toxins Abbreviations: 3-MA, 3-methyladenine; D, knockout; AO, acridine orange; ATF4, activating transcription factor 4; ATG, autophagy-related; Baf A1, bafilomycin A1; BECN1, Beclin 1, autophagy-related; CASP3, caspase 3, apoptosis-related cysteine peptidase; DDIT3, DNA-damage-inducible transcript 3; EHEC O157, Escherichia coli O157:H7; FACS, fluorescence activated cell sorting; MAP1LC3B, microtubule-associated protein 1 light chain 3 beta; MAPK, mitogen-activated protein kinase; MDC, monodansylcadaverine; NUPR1, nuclear protein, transcriptional regulator, 1; PBS, phosphate-buffered saline; PARP1, poly (ADP-ribose) polymerase 1; PI, propidium iodide; Stxs, Shiga toxins; Thap, thapsigargin; TEM, transmission electron microscopy; TRIB3, tribbles pseudokinase 3; WT, wild type; Z-VAD, Z-VAD-FMK.Shiga toxins (Stxs) are a family of cytotoxic proteins that lead to the development of bloody diarrhea, hemolyticuremic syndrome, and central nervous system complications caused by bacteria such as S. dysenteriae, E. coli O157:H7 and E. coli O104:H4. Increasing evidence indicates that macroautophagy (autophagy) is a key factor in the cell death induced by Stxs. However, the associated mechanisms are not yet clear. This study showed that Stx2 induces autophagic cell death in Caco-2 cells, a cultured line model of human enterocytes. Inhibition of autophagy using pharmacological inhibitors, such as 3-methyladenine and bafilomycin A 1 , or silencing of the autophagy genes ATG12 or BECN1 decreased the Stx2-induced death in Caco-2 cells. Furthermore, there were numerous instances of dilated endoplasmic reticulum (ER) in the Stx2-treated Caco-2 cells, and repression of ER stress due to the depletion of viable candidates of DDIT3 and NUPR1. These processes led to Stx2-induced autophagy and cell death. Finally, the data showed that the pseudokinase TRIB3-mediated DDIT3 expression and AKT1 dephosphorylation upon ER stress were triggered by Stx2. Thus, the data indicate that Stx2 causes autophagic cell death via the ER stress pathway in intestinal epithelial cells.

show abstract

“…[23][24] Importantly, several bacteria can make use of miRNAs to participate in modulating autophagy by directly targeting autophagy-related genes, such as BECN1, ATG12, RHEB, ATG5, and ATG16L1. [14][15][16]25 Therefore, involvement of miRNAs in regulating autophagy is undoubtedly worth further investigation. In our model, B. pseudomallei infection increased 3 novel miRNAs, MIR4458, MIR4667-5p and MIR4668-5p, by different time course and spatial expression patterns.…”

Section: Discussionmentioning

confidence: 99%

“…Growing evidence has indicated that dysregulated miRNAs expression is associated with the evasion of autophagy, with several intracellular bacteria. [14][15][16][17] Thus, understanding the molecular mechanisms of autophagy modulation in host response to B. pseudomallei infection is crucial to current and future therapeutic approaches.…”

Section: Introductionmentioning

confidence: 99%

Burkholderia pseudomallei survival in lung epithelial cells benefits from miRNA-mediated suppression of ATG10

Yao

Zhu

et al. 2015

Autophagy

Self Cite

View full text Add to dashboard Cite

(2015) Burkholderiapseudomallei survival in lung epithelial cells benefits from miRNA-mediated suppression of ATG10, Autophagy, 11:8, 1293-1307, DOI: 10.1080/15548627.2015 Keywords: ATG10, autophagy, Burkholderia pseudomallei, DNA methylation, MIR4458, MIR4667-5p, MIR4668-5pAbbreviations: 3-MA, 3-methyladenine; 3 0 UTR, 3 0 -untranslated region; 5-Aza-CdR, 5-aza-2 0 -deoxycytidine; ACTB, actin, b; ATG4C, autophagy-related 4C, cysteine peptidase; ATG5, autophagy-related 5; ATG10, autophagy-related 10; ATG12, autophagyrelated 12; B. pseudomallei, Burkholderia pseudomallei; CFU, colony forming unit; CQ, chloroquine; DNMT1, DNA (cytosine-5-)-methyltransferase 1; DRAM2, DNA-damage regulated autophagy modulator 2; MAP1LC3B, microtubule-associated protein 1 light chain 3 b; miRNAs, microRNAs; MOI, multiplicity of infection; MSP, methylation-specific PCR; PBS, phosphate-buffered saline; p.i., postinfection; Rapa, rapamycin; siRNA, small interfering RNA; SQSTM1, sequestosome 1; TEM, transmission electron microscopy.Burkholderia pseudomallei is the causative agent of melioidosis, a disease with high mortality, which is prevalent in tropical regions of the world. A recent study shows that B. pseudomallei can survive inside mammalian cells because of its ability to actively evade cell autophagy. However, the underlying mechanisms remain unclear. In the present study, based on microarray screening, we found that ATG10 was downregulated following B. pseudomallei infection in A549 human lung epithelial cells. Forced expression of ATG10 accelerated the elimination of intracellular B. pseudomallei by enhancing the process of autophagy. Moreover, MIR4458, MIR4667-5p, and MIR4668-5p were found, by microarray screening, to be upregulated in response to B. pseudomallei infection. These 3 novel miRNAs, MIR4458, MIR4667-5p, and MIR4668-5p, targeted to the 3 0 -untranslated region of ATG10 in different time-course and spatial manners. Upregulation of these miRNAs reduced the level of ATG10 and inhibited autophagy, leading to increasing survival rate of intracellular B. pseudomallei. Furthermore, the increase of these miRNAs was correlated with the reduced promoter methylation status in A549 cells in response to B. pseudomallei infection. Our results reveal that 3 novel miRNAs regulate autophagymediated elimination of B. pseudomallei by targeting ATG10, and provide potential targets for clinical treatment.

show abstract

Compromised autophagy byMIR30Bbenefits the intracellular survival ofHelicobacter pylori

Cited by 123 publications

References 41 publications

Helicobacter pylori Infection in a Pig Model Is Dominated by Th1 and Cytotoxic CD8⁺T Cell Responses

Helicobacter pylori Infection in a Pig Model Is Dominated by Th1 and Cytotoxic CD8⁺T Cell Responses

Shiga toxins induce autophagic cell death in intestinal epithelial cells via the endoplasmic reticulum stress pathway

Burkholderia pseudomallei survival in lung epithelial cells benefits from miRNA-mediated suppression of ATG10

Contact Info

Product

Resources

About

Compromised autophagy byMIR30Bbenefits the intracellular survival ofHelicobacter pylori

Cited by 123 publications

References 41 publications

Helicobacter pylori Infection in a Pig Model Is Dominated by Th1 and Cytotoxic CD8+T Cell Responses

Helicobacter pylori Infection in a Pig Model Is Dominated by Th1 and Cytotoxic CD8+T Cell Responses

Shiga toxins induce autophagic cell death in intestinal epithelial cells via the endoplasmic reticulum stress pathway

Burkholderia pseudomallei survival in lung epithelial cells benefits from miRNA-mediated suppression of ATG10

Contact Info

Product

Resources

About

Helicobacter pylori Infection in a Pig Model Is Dominated by Th1 and Cytotoxic CD8⁺T Cell Responses

Helicobacter pylori Infection in a Pig Model Is Dominated by Th1 and Cytotoxic CD8⁺T Cell Responses