Cellular polarity asymmetrically functionalizes pathogen recognition receptor-mediated intrinsic immune response in human intestinal epithelium cells

SummaryIntestinal epithelial cells (IECs) act as a physical barrier separating the commensal-containing intestinal tract from the sterile interior. These cells have found a complex balance allowing them to be prepared for pathogen attacks while still tolerating the presence of bacteria/viral stimuli present in the lumen of the gut. Using primary human IECs, we probed the mechanisms, which allow for such a tolerance. We discovered that viral infection emanating from the basolateral side of IECs elicited a stronger intrinsic immune response as compared to lumenal apical infection. We determined that this asymmetric immune response was driven by the clathrin-sorting adapter AP-1B which mediates the polarized sorting of Toll-like receptor 3 (TLR3) toward the basolateral side of IECs. Mice and human IECs lacking AP-1B showed an exacerbated immune response following apical stimulation. Together these results suggest a model where the cellular polarity program plays an integral role in the ability of IECs to partially tolerate apical commensals while remaining fully responsive against invasive basolateral pathogens.

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Single-cell transcriptomics reveals immune response of intestinal cell types to viral infection

10.1101/2020.08.19.255893 ◽

2020 ◽

Cited By ~ 1

Author(s):

Sergio Triana ◽

Megan L. Stanifer ◽

Mohammed Shahraz ◽

Markus Mukenhirn ◽

Carmon Kee ◽

...

Keyword(s):

Immune Response ◽

Single Cell ◽

Cell Lineage ◽

Enteric Virus ◽

Cell Types ◽

Intestinal Cell ◽

Intestinal Epithelial ◽

Proliferating Cells ◽

Interferon Stimulated Genes ◽

Human Intestinal Epithelium

AbstractHuman intestinal epithelial cells form a primary barrier protecting us from pathogens, yet only limited knowledge is available about individual contribution of each cell type to mounting an immune response against infection. Here, we developed a pipeline combining single-cell RNA-Seq and highly-multiplex RNA imaging and applied it to human intestinal organoids infected with human astrovirus, a model human enteric virus. We found that interferon controls the infection and that astrovirus infects all major cell types and lineages with a preferential infection of proliferating cells. Intriguingly, each intestinal epithelial cell lineage has a unique basal expression of interferon-stimulated genes and, upon astrovirus infection, undergoes an antiviral transcriptional reprogramming by upregulating distinct sets of interferon-stimulated genes. These findings suggest that in the human intestinal epithelium, each cell lineage plays a unique role in resolving virus infection. Our pipeline can be applicable to other organoids and viruses, opening new avenues to unravel roles of individual cell types in viral pathogenesis.

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Type F scavenger receptor expressed by endothelial cells (SREC)-II from Epinephelus coioides is a potential pathogen recognition receptor in the immune response to Vibrio parahaemolyticus infection

Fish & Shellfish Immunology ◽

10.1016/j.fsi.2019.12.086 ◽

2020 ◽

Vol 98 ◽

pp. 262-270

Author(s):

Xifeng Qiao ◽

Pingchao Li ◽

Jianan He ◽

Zeshu Yu ◽

Jiaxing Chen ◽

...

Keyword(s):

Immune Response ◽

Endothelial Cells ◽

Vibrio Parahaemolyticus ◽

Scavenger Receptor ◽

Epinephelus Coioides ◽

Pathogen Recognition ◽

Potential Pathogen ◽

Pathogen Recognition Receptor ◽

Recognition Receptor

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Role of redox systems on Fe3+ uptake by transformed human intestinal epithelial (Caco-2) cells

AJP Cell Physiology ◽

10.1152/ajpcell.1994.267.6.c1582 ◽

1994 ◽

Vol 267 (6) ◽

pp. C1582-C1588 ◽

Cited By ~ 35

Author(s):

M. T. Nunez ◽

X. Alvarez ◽

M. Smith ◽

V. Tapia ◽

J. Glass

Keyword(s):

Plasma Membrane ◽

Transepithelial Transport ◽

Intestinal Epithelial ◽

Parallel Mechanisms ◽

Redox Systems ◽

Basolateral Side ◽

Fe Uptake ◽

Human Intestinal Epithelium ◽

Reduction Capacity

Caco-2 cells were used as a model of human intestinal epithelium to investigate the role of redox systems in transepithelial transport of 59Fe3+. The cells reduced Fe3+ present in the apical medium; the reduction was 50% inhibited by adriamycin and p-chloromercuribenzoate. Addition of [14C]ascorbate to the basolateral medium resulted in accumulation of 14C radioactivity in both cells and apical medium; apical radioactivity increased with time and was probably caused by paracellular flux. The cells provided Fe3+ reduction capacity to the apical incubation medium. Addition of ascorbate to the basolateral medium increased this reduction capacity 2-fold and the cellular uptake of 59Fe3+ 1.8-fold. Adriamycin significantly inhibited both cellular 59Fe uptake and Fe transport into the basolateral side. The results indicate that Caco-2 cells reduce apical Fe3+ by two parallel mechanisms: by a plasma membrane ferrireductase and by the secretion of reductants of either cellular or basolateral origin. The data support a model for Fe3+ intestinal absorption in which cell-mediated Fe3+ reduction occurs before cellular Fe uptake.

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Search for Compounds Suppressing Intestinal α-Glucosidase Expression in Caco-2 Cells

ICONIET PROCEEDING ◽

10.33555/iconiet.v2i2.18 ◽

2019 ◽

Vol 2 (2) ◽

pp. 96-101

Author(s):

Kota Noda ◽

Eisuke Kato ◽

Jun Kawabata

Keyword(s):

Blood Glucose ◽

Intestinal Tract ◽

Cell Model ◽

Epigallocatechin Gallate ◽

Calluna Vulgaris ◽

Active Principle ◽

Intestinal Epithelial ◽

Mrna Expression Level ◽

Epicatechin Gallate ◽

Control Post

Diabetes is a chronic disease characterized by elevated blood glucose level.Reducing carbohydrate absorption from the intestinal tract is an effective strategy to control post-meal blood glucose level. Inhibition of intestinal α-glucosidase, involved in digestion of carbohydrates, is known as an approach to accomplish this. On the other hand, reduction of α-glucosidase amount is expected to work in the similar manner. However, none of the previousstudy pursues this approach. A convenient assay was developed to evaluate α-glucosidase amount employing Caco-2 cells, the intestinal epithelial cell model reported to express α-glucosidase. Sixty plants were screened and two candidate plants, Calluna vulgaris and Perilla frutescens var. crispa were found to reduce α-glucosidase expression. C. vulgaris extract was subjected to activity guided isolation. Proanthocyanidin was identified as the active principle which was analyzed by thiol decomposition to reveal the components as a mixture ofcatechin, epicatechin, epigallocatechin, and A type procyanidin dimer. The proanthocyanidin suppressed about 30% of α-glucosidase amount evaluated through convenient assay, and suppressed bulk of mRNA expression level of sucrase-isomaltase (SI) at 0.125 mg/mL. Several flavan-3-ol monomers were also tested, and epicatechin gallate and epigallocatechin gallate were found to suppress α-glucosidase amount significantly.

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Peptidomimetic 1-Benzyl-5-methyl-4-(n-octylamino)pyrimidin-2(1H)-one Showed Cardioprotection Effect in a Myocardial Ischemia (MI) Mouse Model

Proceedings ◽

10.3390/proceedings2019022072 ◽

2019 ◽

Vol 22 (1) ◽

pp. 72

Author(s):

Lena Trifonov ◽

Vadim Nudelman ◽

Michael Zhenin ◽

Guy Cohen ◽

Krzysztof Jozwiak ◽

...

Keyword(s):

Immune Response ◽

Pattern Recognition ◽

Myocardial Ischemia ◽

Mouse Model ◽

Innate Immune Response ◽

Pattern Recognition Receptor ◽

Innate Immune ◽

Microbial Pathogens ◽

Toll Like Receptors ◽

Recognition Receptor

TLR4, a member of the toll-like receptors (TLRs) family, serves as a pattern recognition receptor in the innate immune response to different microbial pathogens. [...]

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Protective Effects of Lactoferrin against SARS-CoV-2 Infection In Vitro

Nutrients ◽

10.3390/nu13020328 ◽

2021 ◽

Vol 13 (2) ◽

pp. 328 ◽

Cited By ~ 1

Author(s):

Claudio Salaris ◽

Melania Scarpa ◽

Marina Elli ◽

Alice Bertolini ◽

Simone Guglielmetti ◽

...

Keyword(s):

Immune Response ◽

Epithelial Cells ◽

Intestinal Epithelial Cells ◽

Plaque Assay ◽

Immune Response Gene ◽

Intestinal Epithelial ◽

Antiviral Immune Response ◽

Qrt Pcr ◽

Anti Inflammatory

SARS-CoV-2 is a newly emerging virus that currently lacks curative treatments. Lactoferrin (LF) is a naturally occurring non-toxic glycoprotein with broad-spectrum antiviral, immunomodulatory and anti-inflammatory effects. In this study, we assessed the potential of LF in the prevention of SARS-CoV-2 infection in vitro. Antiviral immune response gene expression was analyzed by qRT-PCR in uninfected Caco-2 intestinal epithelial cells treated with LF. An infection assay for SARS-CoV-2 was performed in Caco-2 cells treated or not with LF. SARS-CoV-2 titer was determined by qRT-PCR, plaque assay and immunostaining. Inflammatory and anti-inflammatory cytokine production was determined by qRT-PCR. LF significantly induced the expression of IFNA1, IFNB1, TLR3, TLR7, IRF3, IRF7 and MAVS genes. Furthermore, LF partially inhibited SARS-CoV-2 infection and replication in Caco-2 intestinal epithelial cells. Our in vitro data support LF as an immune modulator of the antiviral immune response with moderate effects against SARS-CoV-2 infection.

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Arctigenin fromFructus Arctii(Seed of Burdock) Reinforces Intestinal Barrier Function in Caco-2 Cell Monolayers

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/368105 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Hee Soon Shin ◽

Sun Young Jung ◽

Su Yeon Back ◽

Jeong-Ryong Do ◽

Dong-Hwa Shon

Keyword(s):

Barrier Function ◽

Active Component ◽

Inflammatory Diseases ◽

Intestinal Barrier ◽

Transepithelial Electrical Resistance ◽

Intestinal Barrier Function ◽

Intestinal Epithelial ◽

Traditional Herbal Medicine ◽

Cell Monolayers ◽

Basolateral Side

Fructus Arctiiis used as a traditional herbal medicine to treat inflammatory diseases in oriental countries. This study aimed to investigate effect ofF. Arctiiextract on intestinal barrier function in human intestinal epithelial Caco-2 cells and to reveal the active component ofF. Arctii. We measured transepithelial electrical resistance (TEER) value (as an index of barrier function) and ovalbumin (OVA) permeation (as an index of permeability) to observe the changes of intestinal barrier function. The treatment ofF. Arctiiincreased TEER value and decreased OVA influx on Caco-2 cell monolayers. Furthermore, we found that arctigenin as an active component ofF. Arctiiincreased TEER value and reduced permeability of OVA from apical to the basolateral side but not arctiin. In the present study, we revealed thatF. Arctiicould enhance intestinal barrier function, and its active component was an arctigenin on the functionality. We expect that the arctigenin fromF. Arctiicould contribute to prevention of inflammatory, allergic, and infectious diseases by reinforcing intestinal barrier function.

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Harnessing the Induction of CD8+ T-Cell Responses Through Metabolic Regulation by Pathogen-Recognition-Receptor Triggering in Antigen Presenting Cells

Frontiers in Immunology ◽

10.3389/fimmu.2018.02372 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 11

Author(s):

Francesco Nicoli ◽

Stéphane Paul ◽

Victor Appay

Keyword(s):

T Cell ◽

Metabolic Regulation ◽

T Cell Responses ◽

Antigen Presenting Cells ◽

Cd8 T Cell ◽

Pathogen Recognition ◽

Cell Responses ◽

Antigen Presenting ◽

Pathogen Recognition Receptor ◽

Recognition Receptor

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Bacteriophage EK99P-1 Alleviates Enterotoxigenic Escherichia Coli K99-Induced Barrier Dysfunction and Inflammation

10.21203/rs.3.rs-850419/v2 ◽

2021 ◽

Author(s):

Narae Kim ◽

Min jeong Gu ◽

Yoon-Chul Kye ◽

Young-Jun Ju ◽

Rira Hong ◽

...

Keyword(s):

Immune Cell ◽

Inflammatory Responses ◽

Intestinal Barrier ◽

Enterotoxigenic Escherichia Coli ◽

Intestinal Epithelial ◽

Barrier Dysfunction ◽

Barrier Disruption ◽

Host Immune Responses ◽

Basolateral Side ◽

Potential Alternative

Abstract Bacteriophages have long been used as a potential alternative to antibiotics for livestock due to their ability to specifically kill ETEC, which are a major cause of diarrhea in piglets. However, the control of ETEC infection by phages within intestinal epithelial cells, and their relationship with host immune responses, remain poorly understood. In this study, we evaluated the effect of phage EK99P-1 against ETEC K99-infected IPEC-J2. Phage EK99P-1 prevented ETEC K99-induced barrier disruption by attenuating the increased permeability mediated by the loss of tight junction proteins such as ZO-1, occludin, and claudin-3. ETEC K99-induced inflammatory responses, such as IL-8 secretion, were decreased by treatment with phage EK99P-1. We used a IPEC-J2/PBMC Transwell co-culture system to investigate whether the modulation of barrier disruption and chemokine secretion by phage EK99P-1 in ETEC K99-infected IPEC-J2 would influence basolateral immune cells. The results showed that phage EK99P-1 reduced the mRNA expression of ETEC K99-induced pro-inflammatory cytokines, IL-1β and IL-8, from PBMC collected on the basolateral side. Together, these results suggest that phage EK99P-1 prevented ETEC K99-induced barrier dysfunction in IPEC-J2 and alleviated inflammation caused by ETEC K99 infection. Reinforcement of the intestinal barrier by phage EK99P-1 also modulates the immune cell inflammatory response.

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