scholarly journals Immunobiotic Strains Modulate Toll-Like Receptor 3 Agonist Induced Innate Antiviral Immune Response in Human Intestinal Epithelial Cells by Modulating IFN Regulatory Factor 3 and NF-κB Signaling

2019 ◽  
Vol 10 ◽  
Author(s):  
Paulraj Kanmani ◽  
Hojun Kim
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Toll Like Receptor ◽  
Regulatory Factor ◽  
Antiviral Immune Response ◽  
Human Intestinal Epithelial Cells

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

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 328 ◽  
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.

Flagellin-induced tolerance of the Toll-like receptor 5 signaling pathway in polarized intestinal epithelial cells

2007 ◽  
Vol 292 (3) ◽  
pp. G767-G778 ◽  
Author(s):  
Jun Sun ◽  
Pamela E. Fegan ◽  
Anjali S. Desai ◽  
James L. Madara ◽  
Michael E. Hobert
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Prior Exposure ◽  
Intestinal Epithelial ◽  
Toll Like Receptor ◽  
Proinflammatory Response ◽  
Gram Negative ◽  
Human Intestinal Epithelial Cells ◽  
Induced Tolerance ◽  
Toll Like Receptor 5

Salmonella typhimurium is a gram-negative enteric pathogen that invades the mucosal epithelium and is associated with diarrheal illness in humans. Flagellin from S. typhimurium and other gram-negative bacteria has been shown to be the predominant proinflammatory mediator through activation of the basolateral Toll-like receptor 5 (TLR5). Recent evidence has shown that prior exposure can render immune cells tolerant to subsequent challenges by TLR ligands. Accordingly, we examined whether prior exposure to purified flagellin would render human intestinal epithelial cells insensitive to future contact. We found that flagellin-induced tolerance is common to polarized epithelial cells and prevents further activation of proinflammatory signaling cascades by both purified flagellin and Salmonella bacteria but does not affect TNF-α stimulation of the same pathways. Flagellin tolerance is a rapid process that does not require protein synthesis, and that occurs within 1 to 2 h of flagellin exposure. Prolonged flagellin exposure blocks activation of the NF-κB, MAPK, and phosphoinositol 3-kinase signaling pathways and results in the internalization of a fraction of the basolateral TLR5 without affecting the polarity or total expression of TLR5. After removal of flagellin, cells require more than 24 h to fully recover their ability to mount a normal proinflammatory response. We have found that activation of phosphoinositol 3-kinase and Akt by flagellin has a small damping effect in the early stages of flagellin signaling but is not responsible for tolerance. Our study indicates that inhibition of TLR5-associated IL-1 receptor-associated kinase-4 activity occurs during the development of flagellin tolerance and is likely to be the cause of tolerance.

scholarly journals Lactobacillus delbrueckii CRL 581 Differentially Modulates TLR3-Triggered Antiviral Innate Immune Response in Intestinal Epithelial Cells and Macrophages

2021 ◽  
Vol 9 (12) ◽  
pp. 2449
Author(s):  
Mariano Elean ◽  
Leonardo Albarracin ◽  
Kohtaro Fukuyama ◽  
Binghui Zhou ◽  
Mikado Tomokiyo ◽  
...  
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Innate Immune Response ◽  
Intestinal Epithelial Cells ◽  
Starter Culture ◽  
Innate Immune ◽  
Lactobacillus Delbrueckii ◽  
Poly I:C ◽  
Intestinal Epithelial ◽  
Antiviral Immune Response

Lactobacillus delbrueckii subsp. lactis CRL 581 beneficially modulates the intestinal antiviral innate immune response triggered by the Toll-like receptor 3 (TLR3) agonist poly(I:C) in vivo. This study aimed to characterize further the immunomodulatory properties of the technologically relevant starter culture L. delbrueckii subsp. lactis CRL 581 by evaluating its interaction with intestinal epithelial cells and macrophages in the context of innate immune responses triggered by TLR3. Our results showed that the CRL 581 strain was able to adhere to porcine intestinal epithelial (PIE) cells and mucins. The CRL 581 strain also augmented the expression of antiviral factors (IFN-α, IFN-β, Mx1, OAS1, and OAS2) and reduced inflammatory cytokines in PIE cells triggered by TLR3 stimulation. In addition, the influence of L. delbrueckii subsp. lactis CRL 581 on the response of murine RAW macrophages to the activation of TLR3 was evaluated. The CRL 581 strain was capable of enhancing the expression of IFN-α, IFN-β, IFN-γ, Mx1, OAS1, TNF-α, and IL-1β. Of note, the CRL 581 strain also augmented the expression of IL-10 in macrophages. The results of this study show that the high proteolytic strain L. delbrueckii spp. lactis CRL 581 was able to beneficially modulate the intestinal innate antiviral immune response by regulating the response of both epithelial cells and macrophages relative to TLR3 activation.

scholarly journals Campylobacter-Induced Interleukin-8 Secretion in Polarized Human Intestinal Epithelial Cells Requires Campylobacter-Secreted Cytolethal Distending Toxin- and Toll-Like Receptor-Mediated Activation of NF-κB

2008 ◽  
Vol 76 (10) ◽  
pp. 4498-4508 ◽  
Author(s):  
Jie Zheng ◽  
Jianghong Meng ◽  
Shaohua Zhao ◽  
Ruby Singh ◽  
Wenxia Song
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelium ◽  
Intestinal Epithelial Cells ◽  
Interleukin 8 ◽  
Cytolethal Distending Toxin ◽  
Intestinal Epithelial ◽  
Toll Like Receptor ◽  
T84 Cells ◽  
Human Intestinal Epithelial Cells ◽  
Tnf Α

ABSTRACT Campylobacter jejuni and Campylobacter coli colonize and infect the intestinal epithelium and cause acute inflammatory diarrhea. The intestinal epithelium serves as a physical barrier to, and a sensor of, bacterial infection by secreting proinflammatory cytokines. This study examined the mechanisms for Campylobacter-induced secretion of the proinflammatory chemokine interleukin-8 (IL-8) by using polarized T84 human colonic epithelial cells as a model. C. jejuni increased the secretion of both IL-8 and tumor necrosis factor alpha (TNF-α) in polarized epithelial cells. However, the increase in IL-8 secretion was independent of Campylobacter-stimulated TNF-α secretion. Polarized T84 cells secreted IL-8 predominantly to the basolateral medium independently of the inoculation direction. While there was a significant correlation between the levels of IL-8 secretion and Campylobacter invasion, all 11 strains tested increased IL-8 secretion by polarized T84 cells despite their differences in adherence, invasion, and transcytosis efficiencies. Cell-free supernatants of Campylobacter-T84-cell culture increased IL-8 secretion to levels similar to those induced by live bacterial inoculation. The ability of the supernatant to induce IL-8 secretion was reduced by flagellum and cytolethal distending toxin (CDT) gene mutants, treatment of the supernatant with protease K or heat, or treatment of T84 cells with the Toll-like receptor (TLR) inhibitor MyD88 inhibitory peptide or chloroquine. NF-κB inhibitors or cdtB mutation plus MyD88 inhibitor, but not flaA cdtB double mutations, abolished the ability of the supernatant to induce IL-8 secretion. Taken together, our results demonstrate that Campylobacter-induced IL-8 secretion requires functional flagella and CDT and depends on the activation of NF-κB through TLR signaling and CDT in human intestinal epithelial cells.

scholarly journals Single-cell analyses reveal SARS-CoV-2 interference with intrinsic immune response in the human gut

2020 ◽  
Author(s):  
Sergio Triana ◽  
Camila Metz Zumaran ◽  
Carlos Ramirez ◽  
Carmon Kee ◽  
Patricio Doldan ◽  
...  
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Intestinal Epithelium ◽  
Intestinal Epithelial Cells ◽  
List Type ◽  
Intestinal Epithelial ◽  
Human Gut ◽  
Interferon Stimulated Genes ◽  
Human Intestinal Epithelial Cells ◽  
Infected Cells

AbstractObjectiveExacerbated pro-inflammatory immune response contributes to COVID-19 pathology. Despite the evidence about SARS-CoV-2 infecting the human gut, little is known about the importance of the enteric phase of SARS-CoV-2 for the viral lifecycle and for the development of COVID-19-associated pathologies. Similarly, it remains unknown whether the innate immune response triggered in this organ to combat viral infection is similar or distinct compared to the one triggered in other organs.DesignWe exploited human ileum- and colon-derived organoids as a non-transformed culture model supporting SARS-CoV-2 infection. We characterized the replication kinetics of SARS-CoV-2 in intestinal epithelial cells and correlated the expression of the viral receptor ACE2 with infection. We performed conventional and targeted single-cell transcriptomics and multiplex single-molecule RNA fluorescence in situ hybridization and used IFN-reporter bioassays to characterize the response of primary human intestinal epithelial cells to SARS-CoV-2 infection.ResultsWe identified a subpopulation of enterocytes as the prime target of SARS-CoV-2. We found the lack of positive correlation between susceptibility to infection and the expression of ACE2 and revealed that SARS-CoV-2 downregulates ACE2 expression upon infection. Infected cells activated strong proinflammatory programs and produced interferon, while expression of interferon-stimulated genes was limited to bystander cells due to SARS-CoV-2 suppressing the autocrine action of interferon in infected cells.ConclusionOur findings reveal that SARS-CoV-2 curtails the immune response in primary human intestinal epithelial cells to promote its replication and spread and this highlights the gut as a proinflammatory reservoir that should be considered to fully understand SARS-CoV-2 pathogenesis.Significance of the studyWhat is already known about this subject?COVID-19 patients have gastrointestinal symptoms which likely correlates with SARS-CoV-2 infection of the intestinal epitheliumSARS-CoV-2 replicates in human intestinal epithelial cells.Intestinal organoids are a good model to study SARS-CoV-2 infection of the gastrointestinal tractThere is a limited interferon response in human lung epithelial cells upon SARS-CoV-2 infection.What are the new findings?A specific subpopulation of enterocytes are the prime targets of SARS-CoV-2 infection of the human gut.There is a lack of correlation between ACE2 expression and susceptibility to SARS-CoV-2 infection. SARS-CoV-2 downregulates ACE2 expression upon infection.Human intestinal epithelium cells produce interferon upon SARS-CoV-2 infection.Interferon acts in a paracrine manner to induce interferon stimulated genes that control viral infection only in bystander cells.SARS-CoV-2 actively blocks interferon signaling in infected cells.How might it impact on clinical practice in the foreseeable future?The absence of correlation between ACE2 levels and susceptibility suggest that medications influencing ACE2 levels (e.g. high blood pressure drugs) will not make patients more susceptible to SARS-CoV-2 infection.The restricted cell tropism and the distinct immune response mounted by the GI tract, suggests that specific cellular restriction/replication factors and organ specific intrinsic innate immune pathways can represent unique therapeutic targets to treat COVD-19 patients by considering which organ is most infected/impacted by SARS-CoV-2.The strong pro-inflammatory signal mounted by the intestinal epithelium can fuel the systemic inflammation observed in COVID-19 patients and is likely participating in the lung specific pathology.

Sign in / Sign up

Export Citation Format

Share Document