scholarly journals The Dual Tropism of Noroviruses

2018 ◽  
Vol 92 (16) ◽  
Author(s):  
Christiane E. Wobus
Keyword(s):  
Epithelial Cells ◽  
Rna Viruses ◽  
Intestinal Epithelial Cells ◽  
Mammalian Species ◽  
Cell Types ◽  
Economic Losses ◽  
Cell Tropism ◽  
Intestinal Epithelial ◽  
Complex Cell ◽  
Significant Morbidity

ABSTRACTNoroviruses are highly prevalent enteric RNA viruses. Human noroviruses (HuNoVs) cause significant morbidity, mortality, and economic losses worldwide. Infections also occur in other mammalian species, including mice. Despite the discovery of the first norovirus in 1972, the viral tropism has long remained an enigma. A long-held assumption was that these viruses infect intestinal epithelial cells. Recent data support a more complex cell tropism of epithelial and nonepithelial cell types.

scholarly journals Rotavirus VP3 targets MAVS for degradation to inhibit type III interferon expression in intestinal epithelial cells

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Siyuan Ding ◽  
Shu Zhu ◽  
Lili Ren ◽  
Ningguo Feng ◽  
Yanhua Song ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Mammalian Species ◽  
Intestinal Epithelial ◽  
Structural Protein ◽  
Severe Diarrhea ◽  
Multiple Strategies ◽  
Type Iii Interferon ◽  
Proline Rich Region

Rotaviruses (RVs), a leading cause of severe diarrhea in young children and many mammalian species, have evolved multiple strategies to counteract the host innate immunity, specifically interferon (IFN) signaling through RV non-structural protein 1 (NSP1). However, whether RV structural components also subvert antiviral response remains under-studied. Here, we found that MAVS, critical for the host RNA sensing pathway upstream of IFN induction, is degraded by the RV RNA methyl- and guanylyl-transferase (VP3) in a host-range-restricted manner. Mechanistically, VP3 localizes to the mitochondria and mediates the phosphorylation of a previously unidentified SPLTSS motif within the MAVS proline-rich region, leading to its proteasomal degradation and blockade of IFN-λ production in RV-infected intestinal epithelial cells. Importantly, VP3 inhibition of MAVS activity contributes to enhanced RV replication and to viral pathogenesis in vivo. Collectively, our findings establish RV VP3 as a viral antagonist of MAVS function in mammals and uncover a novel pathogen-mediated inhibitory mechanism of MAVS signaling.

scholarly journals Immunomodulatory Effects of TGF-β Family Signaling within Intestinal Epithelial Cells and Carcinomas

2019 ◽  
Vol 1 (2) ◽  
pp. 290-300
Author(s):  
Paula Marincola Smith ◽  
Anna Means ◽  
R. Beauchamp
Keyword(s):  
Epithelial Cells ◽  
Cytokine Production ◽  
Intestinal Epithelial Cells ◽  
Cell Types ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
Immunomodulatory Effects ◽  
Cellular Functions ◽  
Epithelial Cancers ◽  
Causal Pathways

TGF-β superfamily signaling is responsible for many critical cellular functions including control of cell growth, cell proliferation, cell differentiation, and apoptosis. TGF-β appears to be critical in gastrulation, embryonic development, and morphogenesis, and it retains pleiotropic roles in many adult tissues and cell types in a highly context-dependent manner. While TGF-β signaling within leukocytes is known to have an immunosuppressive role, its immunomodulatory effects within epithelial cells and epithelial cancers is less well understood. Recent data has emerged that suggests TGF-β pathway signaling within epithelial cells may directly modulate pro-inflammatory chemokine/cytokine production and resultant leukocyte recruitment. This immunomodulation by epithelial TGF-β pathway signaling may directly impact tumorigenesis and tumor progression through modulation of the epithelial microenvironment, although causal pathways responsible for such an observation remain incompletely investigated. This review presents the published literature as it relates to the immunomodulatory effects of TGF-β family signaling within intestinal epithelial cells and carcinomas.

Accessibility of glycolipid and oligosaccharide epitopes on rabbit villus and follicle-associated epithelium

2000 ◽  
Vol 278 (6) ◽  
pp. G915-G923 ◽  
Author(s):  
Nicholas J. Mantis ◽  
Andreas Frey ◽  
Marian R. Neutra
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Initial Step ◽  
Cell Types ◽  
Specific Cell ◽  
M Cells ◽  
Intestinal Epithelial ◽  
B Subunit ◽  
Maackia Amurensis ◽  
Maackia Amurensis Lectin

The initial step in many mucosal infections is pathogen attachment to glycoconjugates on the apical surfaces of intestinal epithelial cells. We examined the ability of virus-sized (120-nm) and bacterium-sized (1-μm) particles to adhere to specific glycolipids and protein-linked oligosaccharides on the apical surfaces of rabbit Peyer's patch villus enterocytes, follicle-associated enterocytes, and M cells. Particles coated with the B subunit of cholera toxin, which binds the ubiquitous glycolipid GM1, were unable to adhere to enterocytes or M cells. This confirms that both the filamentous brush border glycocalyx on enterocytes and the thin glycoprotein coat on M cells can function as size-selective barriers. Oligosaccharides containing terminal β(1,4)-linked galactose were accessible to soluble lectin Ricinus communistype I on all epithelial cells but were not accessible to lectin immobilized on beads. Oligosaccharides containing α(2,3)-linked sialic acid were recognized on all epithelial cells by soluble Maackia amurensis lectin II (Mal II). Mal II coated 120-nm (but not 1-μm) particles adhered to follicle-associated enterocytes and M cells but not to villus enterocytes. The differences in receptor availability observed may explain in part the selective attachment of viruses and bacteria to specific cell types in the intestinal mucosa.

scholarly journals Intestinal epithelial CD98 synthesis specifically modulates expression of colonic microRNAs during colitis

2012 ◽  
Vol 302 (11) ◽  
pp. G1282-G1291 ◽  
Author(s):  
Moiz A. Charania ◽  
Saravanan Ayyadurai ◽  
Sarah A. Ingersoll ◽  
Bo Xiao ◽  
Emilie Viennois ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Mirna Expression ◽  
Target Genes ◽  
Immune Cell ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial Cells ◽  
Cell Types ◽  
Intestinal Epithelial ◽  
Small Noncoding Rnas

The transmembrane glycoprotein CD98 is known to be involved in intestinal inflammation. In the present study, we found that CD98 overexpression in intestinal epithelial cells does not normally affect the expression of colonic (epithelial and immune cell) microRNAs (miRNAs), small noncoding RNAs that posttranscriptionally regulate a wide variety of biological processes. However, upon dextran sulfate sodium (DSS) treatment, the expression of several colonic miRNAs, but not miRNAs from other tissues such as liver and spleen, were differentially regulated in mice overexpressing CD98 in epithelial cells compared with wild-type (WT) animals. For example, the level of colonic miRNA 132 was not affected by DSS treatment in WT animals but was upregulated in mice overexpressing CD98 in intestinal epithelial cells. Other colonic miRNAs, including colonic miRNA 23a and 23b, were downregulated in WT animals after DSS treatment but not in colonic epithelial cell CD98-overexpressing mice. Interestingly, the expression of potential miRNA target genes affected intestinal epithelial cells that overexpress CD98 and cell types that did not overexpress CD98 but were in close proximity to CD98-overexpressing intestinal epithelial cells. Taken together, these observations show that the combination of an inflammatory context and intestinal epithelial cell expression of CD98 affects the regulation of miRNA expression in colonic epithelial and immune cells. This is new evidence that protein expression modulates miRNA expression and suggests the existence of regulatory crosstalk between proteins and miRNAs in diseases such as colitis.

scholarly journals T helper cells modulate intestinal stem cell renewal and differentiation

2017 ◽  
Author(s):  
Moshe Biton ◽  
Adam L. Haber ◽  
Semir Beyaz ◽  
Noga Rogel ◽  
Christopher Smillie ◽  
...  
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
Epithelial Cells ◽  
Immune Cell ◽  
Intestinal Epithelial Cells ◽  
Cell Types ◽  
Intestinal Epithelial ◽  
T Helper ◽  
Self Renewal

AbstractIn the small intestine, a cellular niche of diverse accessory cell types supports the rapid generation of mature epithelial cell types through self-renewal, proliferation, and differentiation of intestinal stem cells (ISCs). However, not much is known about interactions between immune cells and ISCs, and it is unclear if and how immune cell dynamics affect eventual ISC fate or the balance between self-renewal and differentiation. Here, we used single-cell RNA-seq (scRNA-Seq) of intestinal epithelial cells (IECs) to identify new mechanisms for ISC–immune cell interactions. Surprisingly, MHC class II (MHCII) is enriched in two distinct subsets of Lgr5+ crypt base columnar ISCs, which are also distinguished by higher proliferation rates. Using co-culture of T cells with intestinal organoids, cytokine stimulations, and in vivo mouse models, we confirm that CD4+ T helper (Th) cells communicate with ISCs and affect their differentiation, in a manner specific to the Th subtypes and their signature cytokines and dependent on MHCII expression by ISCs. Specific inducible knockout of MHCII in intestinal epithelial cells in mice in vivo results in expansion of the ISC pool. Mice lacking T cells have expanded ISC pools, whereas specific depletion of Treg cells in vivo results in substantial reduction of ISC numbers. Our findings show that interactions between Th cells and ISCs mediated via MHCII expressed in intestinal epithelial stem cells help orchestrate tissue-wide responses to external signals.

scholarly journals Polarized fibronectin secretion induced by adenosine regulates bacterial–epithelial interaction in human intestinal epithelial cells

2004 ◽  
Vol 382 (2) ◽  
pp. 589-596 ◽  
Author(s):  
Baljit WALIA ◽  
Florencia E. CASTANEDA ◽  
Lixin WANG ◽  
Vasantha L. KOLACHALA ◽  
Rahul BAJAJ ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Matrix Protein ◽  
Intestinal Epithelial Cells ◽  
Cell Types ◽  
Extracellular Matrix Protein ◽  
Intestinal Epithelial ◽  
T84 Cells ◽  
Multifunctional Protein ◽  
Adenosine Receptor Antagonist ◽  
Apical Compartment

Fibronectin (FN) is a multifunctional protein that plays important roles in many biological processes including cell adhesion and migration, wound healing and inflammation. Cellular FNs are produced by a wide variety of cell types including epithelial cells, which secrete them and often organize them into extensive extracellular matrices at their basal surface. However, regulation of FN synthesis and the polarity of FN secretion by intestinal epithelial cells have not been investigated. In the present study we investigated the role of adenosine, whose levels are up-regulated during inflammation, in modulating FN synthesis, the polarity of FN secretion and the downstream effects of the secreted FN. Polarized monolayers of T84 cells were used as an intestinal epithelial model. Adenosine added to either the apical or basolateral aspect of the cells led to a time- and dose-dependent accumulation of FN in the culture supernatants, polarized to the apical compartment and reached maximal levels 24 h after apical or basolateral addition of adenosine. Confocal microscopy confirmed that FN localized to the apical domain of model intestinal epithelial cells stimulated with apical or basolateral adenosine. The induction of FN was significantly down-regulated in response to the adenosine receptor antagonist alloxazine and was inhibited by cycloheximide. Moreover, adenosine increased FN promoter activity (3.5-fold compared with unstimulated controls) indicating that FN induction is, in part, transcriptionally regulated. Interestingly, we demonstrated that adenosine, as well as apical FN, significantly enhanced the adherence and invasion of Salmonella typhimurium into cultured epithelial cells. In summary, we have shown for the first time that FN, a classic extracellular matrix protein, is secreted into the apical compartment of epithelial cells in response to adenosine. FN may be a critical host factor that modulates adherence and invasion of bacteria, thus playing a key role in mucosal immune responses during inflammation.

scholarly journals Doxorubicin Induces Senescence in Intestinal Epithelial Cells

2021 ◽  
Author(s):  
Mandy Biraud ◽  
Jocsa Cortes ◽  
Paul Cray ◽  
Guy Kunzmann ◽  
Javid Mohammed ◽  
...  
Keyword(s):  
Dna Damage ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Cell Types ◽  
Intestinal Epithelial ◽  
Homogeneous Population ◽  
Doxorubicin Treatment ◽  
Induced Apoptosis

AbstractDoxorubicin treatment induces DNA damage and apoptosis in rapidly dividing cell types like intestinal epithelial cells. This has been demonstrated both in vivo and in vitro. In certain cell types some cells do not undergo DNA damage-induced apoptosis in response to doxorubicin but instead become senescent. Induction of senescence in these cells can lead to dysfunction and chronic inflammation, which can lead to more damage. We questioned whether a single dose of doxorubicin would be able to induce apoptosis and senescence in intestinal epithelial cells in vitro. For these studies, we exposed IEC-6 small intestinal epithelial cells to doxorubicin to evaluate whether senescence is induced in a relatively homogeneous population of intestinal epithelial cells. Although some cells underwent apoptosis, those that did not showed traits of senescence. Our studies showed that doxorubicin treatment increased cell size and increased expression of senescence-associated β-galactosidase. Concomitantly, we observed increased mRNA expression of several genes associated with a senescence-associated secretory phenotype including IL-6, Ptges, Faim2, and Cdkn1a and decreased expression of Sirt1. We also observed release of HMGB1, a cellular alarmin, from treated cells. Together, these data suggest that doxorubicin induces senescence in intestinal epithelial cells. Furthermore, our data indicate that cellular responses to a DNA damaging agent, such as doxorubicin, can differ within a population of cells suggesting differing levels of sensitivity within a relatively homogenous cell population. Further studies are needed to delineate the mechanisms that determine whether a cell moves down an apoptotic or senescent pathway following DNA damage.

scholarly journals Host Cell Tropism Underlies Species Restriction of Human and Bovine Cryptosporidium parvum Genotypes

2004 ◽  
Vol 72 (10) ◽  
pp. 6125-6131 ◽  
Author(s):  
Amna Hashim ◽  
Marguerite Clyne ◽  
Grace Mulcahy ◽  
Donna Akiyoshi ◽  
Rachel Chalmers ◽  
...  
Keyword(s):  
Small Bowel ◽  
Epithelial Cells ◽  
Cryptosporidium Parvum ◽  
Intestinal Epithelial Cells ◽  
Specific Cell ◽  
Cell Tropism ◽  
Intestinal Epithelial ◽  
Genotype I ◽  
Genotype Ii

ABSTRACT It has been recognized recently that human cryptosporidiosis is usually caused by Cryptosporidium parvum genotype I (“human” C. parvum), which is not found in animals. Compared to C. parvum genotype II, little is known of the biology of invasion of the human-restricted C. parvum genotype I. The aims of the present study were (i) to explore and compare with genotype II the pathogenesis of C. parvum genotype I infection by using an established in vitro model of infection and (ii) to examine the possibility that host-specific cell tropism determines species restriction among C. parvum genotypes by using a novel ex vivo small intestinal primary cell model of infection. Oocysts of C. parvum genotypes I and II were used to infect HCT-8 cells and primary intestinal epithelial cells in vitro. Primary cells were harvested from human endoscopic small-bowel biopsies and from bovine duodenum postmortem. C. parvum genotype I infected HCT-8 cells with lower efficiency than C. parvum genotype II. Actin colocalization at the host parasite interface and reduction in levels of invasion after treatment with microfilament inhibitors (cytochalasin B and cytochalasin D) were observed for both genotypes. C. parvum genotype II invaded primary intestinal epithelial cells, regardless of the species of origin. In contrast, C. parvum genotype I invaded only human small-bowel cells. The pathogenesis of C. parvum genotype I differs from C. parvum genotype II. C parvum genotype I does not enter primary bovine intestinal cells, suggesting that the species restriction of this genotype is due to host tissue tropism of the infecting isolate.

scholarly journals Dkk-1 Inhibits Intestinal Epithelial Cell Migration by Attenuating Directional Polarization of Leading Edge Cells

2009 ◽  
Vol 20 (22) ◽  
pp. 4816-4825 ◽  
Author(s):  
Stefan Koch ◽  
Christopher T. Capaldo ◽  
Stanislav Samarin ◽  
Porfirio Nava ◽  
Irmgard Neumaier ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Leading Edge ◽  
Cell Types ◽  
Intestinal Epithelial ◽  
Microtubule Organizing Center ◽  
Organizing Center ◽  
Interfering Rna

Wnt signaling pathways regulate proliferation, motility, and survival in a variety of human cell types. Dickkopf-1 (Dkk-1) is a secreted Wnt antagonist that has been proposed to regulate tissue homeostasis in the intestine. In this report, we show that Dkk-1 is secreted by intestinal epithelial cells after wounding and that it inhibits cell migration by attenuating the directional orientation of migrating epithelial cells. Dkk-1 exposure induced mislocalized activation of Cdc42 in migrating cells, which coincided with a displacement of the polarity protein Par6 from the leading edge. Consequently, the relocation of the microtubule organizing center and the Golgi apparatus in the direction of migration was significantly and persistently inhibited in the presence of Dkk-1. Small interfering RNA-induced down-regulation of Dkk-1 confirmed that extracellular exposure to Dkk-1 was required for this effect. Together, these data demonstrate a novel role of Dkk-1 in the regulation of directional polarization of migrating intestinal epithelial cells, which contributes to the effect of Dkk-1 on wound closure in vivo.

scholarly journals Biosynthesis of endotubin: an apical early endosomal glycoprotein from developing rat intestinal epithelial cells

1998 ◽  
Vol 330 (1) ◽  
pp. 367-373 ◽  
Author(s):  
Katrina ALLEN ◽  
K. Erden GOKAY ◽  
A. Mitchell THOMAS ◽  
A. Becky SPEELMAN ◽  
M. Jean WILSON
Keyword(s):  
Monoclonal Antibody ◽  
Epithelial Cells ◽  
Membrane Protein ◽  
Intestinal Epithelial Cells ◽  
Broad Band ◽  
Cell Types ◽  
Transepithelial Transport ◽  
Type I ◽  
Intestinal Epithelial ◽  
Developing Rat

Endosomes are the site of sorting of internalized receptors and ligands in all cell types and, in polarized cells, the apical endosomal compartment is involved in the selective transepithelial transport of immunoglobulins and growth factors. The biochemical composition of this specialized compartment remains largely unresolved. We have characterized a glycoprotein, called endotubin, that is located in the apical endosomal tubules of developing rat intestinal epithelial cells. A monoclonal antibody against endotubin recognizes a broad band of 55-60 kDa, which upon isoelectric focusing can be resolved into two bands, and a faint band of 140 kDa. Metabolic labelling followed by immunoprecipitation indicates that endotubin is synthesized as a 140 kDa precursor that is cleaved to the 55-60 kDa forms. High pH washing of endosomal membranes removes the 55-60 kDa forms from the membrane, whereas the high-molecular-mass form remains membrane associated and appears to be an integral membrane protein. Immunoblotting with a polyclonal antibody against the putative cytoplasmic tail of the protein identifies a 140 kDa band and a band of 74 kDa, presumably the cleavage product. Immunoprecipitation with antibodies against the 55-60 kDa form results in coprecipitation of a 74 kDa protein, and immunoprecipitation with antibody against the 74 kDa protein results in coprecipitation of the 55-60 kDa form. Epitope mapping of the monoclonal antibody binding site supports a proposed type I membrane protein orientation. We propose that endotubin is proteolytically processed into a heterodimer with the 55-60 kDa fragment remaining membrane-associated through a non-covalent association with the membrane-bound 74 kDa portion of the molecule.

Sign in / Sign up

Export Citation Format

Share Document