scholarly journals Intestinal Epithelial Cells Modulate Antigen-Presenting Cell Responses to Bacterial DNA

2012 ◽  
Vol 80 (8) ◽  
pp. 2632-2644 ◽  
Author(s):  
J. L. Campeau ◽  
S. Y. Salim ◽  
E. J. Albert ◽  
N. Hotte ◽  
K. L. Madsen
Keyword(s):  
T Cells ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Cytokine Secretion ◽  
Intestinal Epithelial ◽  
Bacterial Dna ◽  
Content Type ◽  
Cell Responses ◽  
K Cells ◽  
Antigen Presenting

ABSTRACTIntestinal epithelial cells and antigen-presenting cells orchestrate mucosal innate immunity. This study investigated the role of bacterial DNA in modulating epithelial and bone marrow-derived antigen-presenting cells (BM-APCs) and subsequent T-lymphocyte responses. Murine MODE-K epithelial cells and BM-APCs were treated with DNA from eitherBifidobacterium breveorSalmonella entericaserovar Dublin directly and under coculture conditions with CD4+T cells. Apical stimulation of MODE-K cells withS. Dublin DNA enhanced secretion of cytokines from underlying BM-APCs and induced interleukin-17 (IL-17) and gamma interferon (IFN-γ) secretion from CD4+T cells. Bacterial DNA isolated from either strain induced maturation and increased cytokine secretion from BM-APCs. Conditioned medium fromS. Dublin-treated MODE-K cells elicited an increase in cytokine secretion similar to that seen forS. Dublin DNA. Treatment of conditioned medium from MODE-K cells with RNase and protease prevented theS. Dublin-induced increased cytokine secretion. Oral feeding of mice withB. breveDNA resulted in enhanced levels of colonic IL-10 and transforming growth factor β (TGFβ) compared with what was seen for mice treated withS. Dublin DNA. In contrast, feeding mice withS. Dublin DNA increased levels of colonic IL-17 and IL-12p70. T cells fromS. Dublin DNA-treated mice secreted high levels of IL-12 and IFN-γ compared to controls andB. breveDNA-treated mice. These results demonstrate that intestinal epithelial cells are able to modulate subsequent antigen-presenting and T-cell responses to bacterial DNA with pathogenic but not commensal bacterial DNA inducing effector CD4+T lymphocytes.

scholarly journals Salmonella entericaSerovar Typhimurium Increases Functional PD-L1 Synergistically with Gamma Interferon in Intestinal Epithelial Cells viaSalmonellaPathogenicity Island 2

2018 ◽  
Vol 86 (5) ◽  
pp. e00674-17 ◽  
Author(s):  
J. M. Sahler ◽  
C. R. Eade ◽  
C. Altier ◽  
J. C. March
Keyword(s):  
T Cells ◽  
Epithelial Cells ◽  
Host Cell ◽  
Immune Evasion ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Activated T Cells ◽  
Content Type ◽  
Ifn Γ ◽  
First Time

ABSTRACTNontyphoidal serovars ofSalmonella entericaare pathogenic bacteria that are common causes of food poisoning. WhereasSalmonellamechanisms of host cell invasion, inflammation, and pathogenesis are mostly well established, a new possible mechanism of immune evasion is being uncovered. Programmed death ligand 1 (PD-L1) is an immunosuppressive membrane protein that binds to activated T cells via their PD-1 receptor and thereby halts their activation. PD-L1 expression plays an essential role in the immunological tolerance of self-antigens but is also exploited for immune evasion by pathogen-infected cells and cancer cells. Here, we show for the first time thatSalmonellainfection of intestinal epithelial cells causes the induction of PD-L1. The increased expression of PD-L1 throughSalmonellainfection was seen in both human and rat intestinal epithelial cell lines. We determined that cellular invasion by the bacteria is necessary for PD-L1 induction, potentially indicating thatSalmonellastrains are delivering mediators from inside the host cell that trigger the increased PD-L1 expression. Using knockout mutants, we determined that this effect largely originates from theSalmonellapathogenicity island 2. We also show for the first time in any cell type thatSalmonellacombined with gamma interferon (IFN-γ) causes a synergistic induction of PD-L1. Finally, we show thatSalmonellaplus IFN-γ induction of PD-L1 decreased the cytokine production of activated T cells. UnderstandingSalmonellaimmune evasion strategies could generate new therapeutic targets and help to manipulate PD-L1 expression in other diseases.

scholarly journals IL-17A Reprograms Intestinal Epithelial Cells to Facilitate HIV-1 Replication and Outgrowth in CD4+ T-cells

iScience ◽  
2021 ◽  
pp. 103225
Author(s):  
Tomas Raul Wiche Salinas ◽  
Annie Gosselin ◽  
Laurence Raymond Marchand ◽  
Etiene Moreira Gabriel ◽  
Olivier Tastet ◽  
...  
Keyword(s):  
T Cells ◽  
Epithelial Cells ◽  
Cd4 T Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Hiv 1

scholarly journals Dual Recognition of Sialic Acid and αGal Epitopes by the VP8* Domains of the Bovine Rotavirus G6P[5] WC3 and of Its Mono-reassortant G4P[5] RotaTeq Vaccine Strains

2019 ◽  
Vol 93 (18) ◽  
Author(s):  
Mia Madel Alfajaro ◽  
Ji-Yun Kim ◽  
Laure Barbé ◽  
Eun-Hyo Cho ◽  
Jun-Gyu Park ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Blood Group ◽  
Intestinal Epithelial Cells ◽  
Sialic Acids ◽  
Blood Group Antigens ◽  
Intestinal Epithelial ◽  
Content Type ◽  
Group A Rotaviruses ◽  
Group A ◽  
Small Intestinal

ABSTRACTGroup A rotaviruses, an important cause of severe diarrhea in children and young animals, initiate infection via interactions of the VP8* domain of the VP4 spike protein with cell surface sialic acids (SAs) or histo-blood group antigens (HBGAs). Although the bovine G6P[5] WC3 strain is an important animal pathogen and is also used in the bovine-human reassortant RotaTeq vaccine, the receptor(s) for the VP8* domain of WC3 and its reassortant strains have not yet been identified. In the present study, HBGA- and saliva-binding assays showed that both G6P[5] WC3 and mono-reassortant G4P[5] strains recognized the αGal HBGA. The infectivity of both P[5]-bearing strains was significantly reduced in αGal-free MA-104 cells by pretreatment with a broadly specific neuraminidase or by coincubation with the α2,6-linked SA-specificSambucus nigralectin, but not by the α2,3-linked specific sialidase or byMaackia amurensislectin. Free NeuAc and the αGal trisaccharide also prevented the infectivity of both strains. This indicated that both P[5]-bearing strains utilize α2,6-linked SA as a ligand on MA104 cells. However, the two strains replicated in differentiated bovine small intestinal enteroids and in their human counterparts that lack α2,6-linked SA or αGal HBGA, suggesting that additional or alternative receptors such as integrins, hsp70, and tight-junction proteins bound directly to the VP5* domain can be used by the P[5]-bearing strains to initiate the infection of human cells. In addition, these data also suggested that P[5]-bearing strains have potential for cross-species transmission.IMPORTANCEGroup A rotaviruses initiate infection through the binding of the VP8* domain of the VP4 protein to sialic acids (SAs) or histo-blood group antigens (HBGAs). Although the bovine G6P[5] WC3 strain is an important animal pathogen and is used as the backbone in the bovine-human reassortant RotaTeq vaccine, the receptor(s) for their P[5] VP8* domain has remained elusive. Using a variety of approaches, we demonstrated that the WC3 and bovine-human mono-reassortant G4P[5] vaccine strains recognize both α2,6-linked SA and αGal HBGA as ligands. Neither ligand is expressed on human small intestinal epithelial cells, explaining the absence of natural human infection by P[5]-bearing strains. However, we observed that the P[5]-bearing WC3 and G4P[5] RotaTeq vaccine strains could still infect human intestinal epithelial cells. Thus, the four P[5] RotaTeq vaccine strains potentially binding to additional alternative receptors may be efficient and effective in providing protection against severe rotavirus disease in human.

scholarly journals Interleukin-7 Produced by Intestinal Epithelial Cells in Response to Citrobacter rodentium Infection Plays a Major Role in Innate Immunity against This Pathogen

2015 ◽  
Vol 83 (8) ◽  
pp. 3213-3223 ◽  
Author(s):  
Wei Zhang ◽  
Jiang-Yuan Du ◽  
Qing Yu ◽  
Jun-O Jin
Keyword(s):  
Epithelial Cells ◽  
Protective Immunity ◽  
Bacterial Infections ◽  
Intestinal Epithelial Cells ◽  
Intestinal Damage ◽  
Intestinal Epithelial ◽  
Citrobacter Rodentium ◽  
Content Type ◽  
Interleukin 7

Interleukin-7 (IL-7) engages multiple mechanisms to overcome chronic viral infections, but the role of IL-7 in bacterial infections, especially enteric bacterial infections, remains unclear. Here we characterized the previously unexplored role of IL-7 in the innate immune response to the attaching and effacing bacteriumCitrobacter rodentium.C. rodentiuminfection induced IL-7 production from intestinal epithelial cells (IECs). IL-7 production from IECs in response toC. rodentiumwas dependent on gamma interferon (IFN-γ)-producing NK1.1+cells and IL-12. Treatment with anti-IL-7Rα antibody duringC. rodentiuminfection resulted in a higher bacterial burden, enhanced intestinal damage, and greater weight loss and mortality than observed with the control IgG treatment. IEC-produced IL-7 was only essential for protective immunity againstC. rodentiumduring the first 6 days after infection. An impaired bacterial clearance upon IL-7Rα blockade was associated with a significant decrease in macrophage accumulation and activation in the colon. Moreover,C. rodentium-induced expansion and activation of intestinal CD4+lymphoid tissue inducer (LTi) cells was completely abrogated by IL-7Rα blockade. Collectively, these data demonstrate that IL-7 is produced by IECs in response toC. rodentiuminfection and plays a critical role in the protective immunity against this intestinal attaching and effacing bacterium.

scholarly journals CapC, a Novel Autotransporter and Virulence Factor ofCampylobacter jejuni

2018 ◽  
Vol 84 (16) ◽  
Author(s):  
Jai W. Mehat ◽  
Simon F. Park ◽  
Arnoud H. M. van Vliet ◽  
Roberto M. La Ragione
Keyword(s):  
Public Health ◽  
Epithelial Cells ◽  
Campylobacter Jejuni ◽  
Virulence Factor ◽  
Causative Agent ◽  
Galleria Mellonella ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Content Type ◽  
Reduced Adherence

ABSTRACTCampylobacter jejuniis recognized as an important causative agent of bacterial gastroenteritis in the developed world. Despite the identification of several factors contributing to infection, characterization of the virulence strategies employed byC. jejuniremains a significant challenge. Bacterial autotransporter proteins are a major class of secretory proteins in Gram-negative bacteria, and notably, many autotransporter proteins contribute to bacterial virulence. The aim of this study was to characterize theC. jejuni81116 C8J_1278 gene (capC), predicted to encode an autotransporter protein, and examine the contribution of this factor to virulence ofC. jejuni. The predicted CapC protein has a number of features that are consistent with autotransporters, including the N-terminal signal sequence and the C-terminal β-barrel domain and was determined to localize to the outer membrane. Inactivation of thecapCgene inC. jejuni81116 andC. jejuniM1 resulted in reduced insecticidal activity inGalleria mellonellalarvae. Furthermore,C. jejuni capCmutants displayed significantly reduced adherence to and invasion of nonpolarized, partially differentiated Caco-2 and T84 intestinal epithelial cells. Gentamicin treatment showed that the reduced invasion of thecapCmutant is primarily caused by reduced adherence to intestinal epithelial cells, not by reduced invasion capability.C. jejuni capCmutants caused reduced interleukin 8 (IL-8) secretion from intestinal epithelial cells and elicited a significantly diminished immune reaction inGallerialarvae, indicating that CapC functions as an immunogen. In conclusion, CapC is a new virulence determinant ofC. jejunithat contributes to the integral infection process of adhesion to human intestinal epithelial cells.IMPORTANCECampylobacter jejuniis a major causative agent of human gastroenteritis, making this zoonotic pathogen of significant importance to human and veterinary public health worldwide. The mechanisms by whichC. jejuniinteracts with intestinal epithelial cells and causes disease are still poorly understood due, in part, to the heterogeneity ofC. jejuniinfection biology. Given the importance ofC. jejunito public health, the need to characterize novel and existing virulence mechanisms is apparent. The significance of our research is in demonstrating the role of CapC, a novel virulence factor inC. jejunithat contributes to adhesion and invasion of the intestinal epithelium, thereby in part, addressing the dearth of knowledge concerning the factors involved inCampylobacterpathogenesis and the variation observed in the severity of human infection.

scholarly journals The Hemorrhagic Coli Pilus (HCP) of Escherichia coli O157:H7 Is an Inducer of Proinflammatory Cytokine Secretion in Intestinal Epithelial Cells

PLoS ONE ◽  
2010 ◽  
Vol 5 (8) ◽  
pp. e12127 ◽  
Author(s):  
Maria A. Ledesma ◽  
Sara A. Ochoa ◽  
Ariadnna Cruz ◽  
Luz M. Rocha-Ramírez ◽  
Jaime Mas-Oliva ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Epithelial Cells ◽  
Proinflammatory Cytokine ◽  
Intestinal Epithelial Cells ◽  
Cytokine Secretion ◽  
Escherichia Coli O157 ◽  
Intestinal Epithelial
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