scholarly journals Avian [beta]-defensins as antimicrobial and immunomodulatory agents

2018 ◽  
Author(s):  
◽  
Ming Yang
Keyword(s):  
Dendritic Cells ◽  
Antimicrobial Peptides ◽  
Animal Health ◽  
Host Cells ◽  
Manufacturing Cost ◽  
Experimental Conditions ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Immature Dendritic Cells ◽  
Beta Defensins

The increasing prevalence of antibiotic-resistance and lack of effective antibiotics pose a serious threat to animal health and public health. Host antimicrobial peptides (AMPs) show broad-spectrum antimicrobial activity against various microbes with low potential for resistance development, compared to conventional antibiotics, indicating great potentials as therapeutic agents. Despite such promise, several limitations hinder the application of AMPs in the clinic, including high manufacturing cost, cytotoxicity, and stability in physiological conditions. New strategies are needed to solve those problems for their application. Avian beta-defensins (AvBD) are small, cationic, antimicrobial peptides. The potential application of AvBDs as antibiotic alternatives against antibiotic-resistant and zoonotic bacterial pathogens has been the subject of interest. In the first study, the biological functions of two AvBDs, AvBD-6 and AvBD-12, were determined under various experimental conditions. The results showed that AvBD-6 (+7) was more potent than AvBD-12 (+1) against E. coli, S. Typhimurium, and S. aureus as well as clinical isolates of extended-spectrum beta-lactamase (ESBL)-producing E. coli and K. pneumoniae. The antibacterial activity of AvBDs was greatly compromised under physiological salt concentrations. Both AvBDs demonstrated mild chemotactic property for chicken macrophages and AvBD-12, at relatively high concentrations, could also induce the migration of murine immature dendritic cells. The chemotactic property required the presence of chemokine receptor 2 (CCR2) on host cells and the conserved disulfide bridges of the peptides. The two AvBDs were nontoxic to CHO-K1, macrophages, or immature dendritic cells.

Microbiota Small RNAs in Inflammatory Bowel Disease

2016 ◽  
Vol 25 (4) ◽  
pp. 509-516 ◽  
Author(s):  
Anca T. Filip ◽  
Ovidiu Balacescu ◽  
Catalin Marian ◽  
Andrei Anghel
Keyword(s):  
Inflammatory Bowel Disease ◽  
Dendritic Cells ◽  
Rna Interference ◽  
Mirna Expression ◽  
Bowel Disease ◽  
B Cell Lymphoma ◽  
Lactobacillus Delbrueckii ◽  
Host Cells ◽  
E Coli ◽  
Inflammatory Bowel

MiRNAs are a class of potential gene regulators of critical importance in Inflammatory Bowel Disease (IBD). This review aims to present the connection between gut microbiota, probiotics administration and microRNA (miRNA) expression in IBD. It also brings into question cross-kingdom RNAi (RNA interference). Not only that gut host cells garden the intestinal microbiome via miRNA, but also strong evidence supports the idea that different species of bacteria have an impact on the intestinal immune response by modulating miRNA expression. Cross-kingdom RNAi refers to RNA silencing signals that travel between two unrelated, interacting organisms. RNAs communication between prokaryotes and eukaryotes (bacteria and nematodes) via RNAs transfer has been proved. Some authors also support the idea that non-coding RNAs are being transferred by bacterial pathogens to the host cells as part of the intracellular infection process. Further studies are required in order to clarify whether the mechanism by which bacteria modulate miRNA expression concerns RNAs transfer. These findings may lead to a different approach to IBD therapy in the future. Abbreviations: AChE: Acetylcholinesterase; AIEC: Adherent-invasive E coli; ATF: Activating transcription factor; Bcl-2: B-cell lymphoma 2; BMDC: Bone marrow-derived dendritic cells; C elegans: Caenorhabditis elegans; CCL: Chemokine C-C motif ligand; CD: Crohn’s disease; CDC42: Cell division control protein 42 homolog; CXCL: Chemokine (C-X-C motif) ligand; DC: Dendritic cells; E Coli: Escherichia coli; EcN: E coli Nissle; EPEC: Entheropathogenic E coli; FOXO3: Forkhead box protein O3; GF: Germ-free; IBD: Inflammatory bowel disease; IECs: Intestinal epithelial cells; IGLC: Immunoglobulin Lambda Constant Region; IkB: Inhibitor of NF-Kb; IL: Interleukin; IRGM: Immunity-related GTPase family M protein; L del: Lactobacillus delbrueckii; LGG: Lactobacillus rhamnosus GG; MAPK: Mitogen-activated protein kinases; miRNA: MicroRNA; mRNA: Messenger RNA; MyD88: Myeloid differentiation primary response gene 88; NF-kB: Nuclear factor kappa B; NOD2: Nucleotide-binding oligomerization domain-containing protein 2; PAR: Partitioning defective protein; RhoB: Ras Homolog Family Member B; RISC: RNA induced silencing complex; RNAi: RNA interference; SHH: Sonic hedgehog (gene); SPF: Specific-pathogen-free; SRNA: Small RNA; STAT3: Signal transducer and activator of transcription 3; TGF: Transforming growth factor; Th17: T helper 17 cells; TJ: Tight junction; TLR: Toll like receptor; TNF: Tumor necrosis factor; UC: Ulcerative colitis; Xcv: Xanthomonas campestris pv. Vesicatoria; ZO-2: Zonula occludens-2.

scholarly journals Th17 T cells and immature dendritic cells are the preferential initial targets after rectal challenge with an SIV-based replication-defective dual-reporter vector

2021 ◽  
Author(s):  
Danijela Maric ◽  
Wesley A. Grimm ◽  
Natalie Greco ◽  
Michael D. McRaven ◽  
Angela J. Fought ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Rectal Mucosa ◽  
Host Cells ◽  
Target Cells ◽  
Receptive Anal Intercourse ◽  
Prevention Strategies ◽  
Immature Dendritic Cells ◽  
Hiv Prevention Strategies ◽  
Dual Reporter

ABSTRACTUnderstanding the earliest events of HIV sexual transmission is critical to develop and optimize HIV prevention strategies. To gain insights into the earliest steps of HIV rectal transmission, including cellular targets, rhesus macaques were intra-rectally challenged with a single-round SIV-based dual reporter that expresses luciferase and iRFP670 upon productive transduction. The vector was pseudotyped with the HIV-1 envelope JRFL. Regions of tissue containing foci of luminescent, transduced cells were identified macroscopically using an in vivo imaging system, and individual transduced cells expressing fluorescent protein were identified and phenotyped microscopically. This system revealed that anal and rectal tissues are both susceptible to transduction 48 hours after the rectal challenge. Detailed phenotypic analysis revealed that on average, 62% of transduced cells are CCR6+ T cells—the vast majority of which express RORγT, a Th17 lineage-specific transcription factor. The second most common target cells were immature dendritic cells at 20%. These two cell types were transduced at the rates that are four to five times higher than their relative abundances indicate. Our work demonstrates that Th17 T and immature dendritic cells are preferential initial targets of HIV/SIV rectal transmission.IMPORTANCEMen and women who participate in unprotected receptive anal intercourse are at high risk for acquiring HIV. While in vitro data have developed a framework for understanding HIV cell tropism, the initial target cells in the rectal mucosa have not been identified. In this study, we identify these early host cells by using an innovative rhesus macaque rectal challenge model and methodology, which we previously developed. Thus, by shedding light on these early HIV/SIV transmission events, this study provides a specific cellular target for future prevention strategies.

scholarly journals The prevalence of extended spectrum bêta-lactamase-producing Escherichia coli isolated in wastewater in relation to patients hospitalized in the city of Meknes in Morocco

2021 ◽  
Vol 319 ◽  
pp. 02014
Author(s):  
Khadija Ouarrak ◽  
Abdelkader Chahlaoui ◽  
Hajar El Omari ◽  
Imane Taha ◽  
Rachid Sammoudi ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Animal Health ◽  
Hospitalized Patients ◽  
Fecal Coliforms ◽  
Resistant Bacteria ◽  
Beta Lactamase ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Extended Spectrum ◽  
The City

The present study was conducted to better understand the specific contingency of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E. coli) isolated from urban waters of Wadi Ouislane of the city of Meknes, compared to isolates from patients hospitalized in the resuscitation department at Mohamed V Hospital in Meknes, Morocco. These antibiotic-resistant bacteria have become ubiquitous in effluents, creating increasing concern about their potential impact on human and animal health and the environment. We took four samples of wastewater representative of a day, effluents of the wadi Ouislane. They were analyzed for indicator germs of fecal pollution, namely total coliforms (TC) and fecal coliforms (FC). Bacteria were enumerated by the dilution-filtration technique and by incorporation in solid medium in supercooling. However, four bacteriological samples, taken for clinical purposes from hospitalized patients, were performed at the medical analysis laboratory of Mohamed V Hospital in Meknes. Analysis of our results showed that ESBL-producing E. coli bacteria isolated from our effluents had the same antibiotic resistance profiles as those from hospitalized patients. Urban wastewater discharges into the environment contribute to the dissemination of extended-spectrum beta-lactamase-producing Escherichia coli that may pose health risks to the population.

scholarly journals Th17 T cells and immature dendritic cells are the preferential initial targets after rectal challenge with an SIV-based replication-defective dual-reporter vector

2021 ◽  
Author(s):  
Danijela Maric ◽  
Wesley A. Grimm ◽  
Natalie Greco ◽  
Michael D. McRaven ◽  
Angela J. Fought ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Rectal Mucosa ◽  
Host Cells ◽  
Target Cells ◽  
Receptive Anal Intercourse ◽  
Prevention Strategies ◽  
Immature Dendritic Cells ◽  
Hiv Prevention Strategies ◽  
Dual Reporter

Understanding the earliest events of HIV sexual transmission is critical to develop and optimize HIV prevention strategies. To gain insights into the earliest steps of HIV rectal transmission, including cellular targets, rhesus macaques were intra-rectally challenged with a single-round SIV-based dual reporter that expresses luciferase and iRFP670 upon productive transduction. The vector was pseudotyped with the HIV-1 envelope JRFL. Regions of tissue containing foci of luminescent, transduced cells were identified macroscopically using an in vivo imaging system, and individual transduced cells expressing fluorescent protein were identified and phenotyped microscopically. This system revealed that anal and rectal tissues are both susceptible to transduction 48 hours after the rectal challenge. Detailed phenotypic analysis revealed that on average, 62% of transduced cells are CCR6 + T cells—the vast majority of which express RORγT, a Th17 lineage-specific transcription factor. The second most common target cells were immature dendritic cells at 20%. These two cell types were transduced at the rates that are four to five times higher than their relative abundances indicate. Our work demonstrates that Th17 T and immature dendritic cells are preferential initial targets of HIV/SIV rectal transmission. IMPORTANCE Men and women who participate in unprotected receptive anal intercourse are at high risk for acquiring HIV. While in vitro data have developed a framework for understanding HIV cell tropism, the initial target cells in the rectal mucosa have not been identified. In this study, we identify these early host cells by using an innovative rhesus macaque rectal challenge model and methodology, which we previously developed. Thus, by shedding light on these early HIV/SIV transmission events, this study provides a specific cellular target for future prevention strategies.

scholarly journals The Inflammatory Response to Enterotoxigenic E. coli and Probiotic E. faecium in a Coculture Model of Porcine Intestinal Epithelial and Dendritic Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Henriette Loss ◽  
Jörg R. Aschenbach ◽  
Karsten Tedin ◽  
Friederike Ebner ◽  
Ulrike Lodemann
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Transforming Growth Factor ◽  
Cell Types ◽  
Inflammasome Activation ◽  
Intestinal Epithelial ◽  
Experimental Conditions ◽  
E Coli ◽  
Coculture Model

The gut epithelium constitutes an interface between the intestinal contents and the underlying gut-associated lymphoid tissue (GALT) including dendritic cells (DC). Interactions of intestinal epithelial cells (IEC) and resident DC are characterized by bidirectional crosstalk mediated by various factors, such as transforming growth factor-β (TGF-β) and thymic stromal lymphopoietin (TSLP). In the present study, we aimed (1) to model the interplay of both cell types in a porcine in vitro coculture consisting of IEC (cell line IPEC-J2) and monocyte-derived DC (MoDC) and (2) to assess whether immune responses to bacteria are altered because of the interplay between IPEC-J2 cells and MoDC. With regard to the latter, we focused on the inflammasome pathway. Here, we propose caspase-13 as a promising candidate for the noncanonical inflammasome activation in pigs. We conducted challenge experiments with enterotoxigenic Escherichia coli (ETEC) and probiotic Enterococcus faecium (E. faecium) NCIMB 10415. As potential mediators of IEC/DC interactions, TGF-β and TSLP were selected for analyses. Cocultured MoDC showed attenuated ETEC-induced inflammasome-related and proinflammatory interleukin (IL)-8 reactions compared with MoDC monocultures. Caspase-13 was more strongly expressed in IPEC-J2 cells cocultured with MoDC and upon ETEC incubation. We found that IPEC-J2 cells and MoDC were capable of releasing TSLP. The latter cells secreted greater amounts of TSLP when cocultured with IPEC-J2 cells. TGF-β was not modulated under the present experimental conditions in either cell types. We conclude that, in the presence of IPEC-J2 cells, porcine MoDC exhibited a more tolerogenic phenotype, which might be partially regulated by autocrine TSLP production. Noncanonical inflammasome signaling appeared to be modulated in IPEC-J2 cells. Our results indicate that the reciprocal interplay of the intestinal epithelium and GALT is essential for promoting balanced immune responses.

Procaryotic Expression of Single-Chain Variable-Fragment (scFv) Antibodies: Secretion in L-Form Cells of Proteus mirabilis Leads to Active Product and Overcomes the Limitations of Periplasmic Expression in Escherichia coli

1998 ◽  
Vol 64 (12) ◽  
pp. 4862-4869 ◽  
Author(s):  
Jörg F. Rippmann ◽  
Michaela Klein ◽  
Christian Hoischen ◽  
Bodo Brocks ◽  
Wolfgang J. Rettig ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Proteus Mirabilis ◽  
Binding Activity ◽  
Host Cells ◽  
Heterologous Proteins ◽  
Single Chain Variable Fragment ◽  
Single Chain ◽  
E Coli ◽  
Active Product ◽  
Periplasmic Expression

ABSTRACT Recently it has been demonstrated that L-form cells ofProteus mirabilis (L VI), which lack a periplasmic compartment, can be efficiently used in the production and secretion of heterologous proteins. In search of novel expression systems for recombinant antibodies, we compared levels of single-chain variable-fragment (scFv) production in Escherichia coliJM109 and P. mirabilis L VI, which express four distinct scFvs of potential clinical interest that show differences in levels of expression and in their tendencies to form aggregates upon periplasmic expression. Production of all analyzed scFvs in E. coli was limited by the severe toxic effect of the heterologous product as indicated by inhibition of culture growth and the formation of insoluble aggregates in the periplasmic space, limiting the yield of active product. In contrast, the L-form cells exhibited nearly unlimited growth under the tested production conditions for all scFvs examined. Moreover, expression experiments with P. mirabilis L VI led to scFv concentrations in the range of 40 to 200 mg per liter of culture medium (corresponding to volume yields 33- to 160-fold higher than those with E. coli JM109), depending on the expressed antibody. In a translocation inhibition experiment the secretion of the scFv constructs was shown to be an active transport coupled to the signal cleavage. We suppose that this direct release of the newly synthesized product into a large volume of the growth medium favors folding into the native active structure. The limited aggregation of scFv observed in the P. mirabilis L VI supernatant (occurring in a first-order-kinetics manner) was found to be due to intrinsic features of the scFv and not related to the expression process of the host cells. The P. mirabilis L VI supernatant was found to be advantageous for scFv purification. A two-step chromatography procedure led to homogeneous scFv with high antigen binding activity as revealed from binding experiments with eukaryotic cells.

Higher CD1a Levels Correlate with PD-L1 Expression and Predict Worse Overall Survival in Triple-Negative Breast Carcinoma

Breast Care ◽  
2021 ◽  
pp. 1-9
Author(s):  
Jian Zheng ◽  
Yuntao Wei ◽  
Xiaoxi Li ◽  
Zhan Shen ◽  
Yong Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Dendritic Cells ◽  
Lymph Node ◽  
Breast Carcinoma ◽  
Triple Negative ◽  
Carcinoma Tissue ◽  
Kaplan Meier ◽  
Immature Dendritic Cells ◽  
Triple Negative Breast Carcinoma ◽  
High Median

Objective: The aim of this study was to measure the expression of PD-L1, CD1a (a marker for immature dendritic cells), and CD83 (a marker for mature dendritic cells) and further examine the associations of PD-L1, CD83, and CD1a with overall survival (OS) in triple-negative breast carcinoma patients. Methods: PD-L1, CD1a, and CD83 expression in breast carcinoma tissues and CD83 expression in lymph node tissues were examined by immunohistochemistry and tissue microarray in 159 patients. Patients were classified into the low, medium, and high PD-L1, CD1a, and CD83 levels. Pearson χ2 test was used to analyze the correlations between PD-L1, CD1a, and CD83. The Kaplan-Meier method was used to calculate the OS. Multivariate analysis was used to identify determinants of 3- and 5-year OS. Results: 25.1, 25.8, and 49.1% of the patients had low, medium, and high PD-L1 levels, respectively. PD-L1 levels significantly correlated with CD1a (r = 0.30409, p < 0.001) and CD83 levels (r = 0.6146, p < 0.001) in breast carcinoma tissue, as well as CD83 levels (r = 0.17508, p = 0.027) in lymph node. The median OS was 83 months (range 12–106), and the 3- and 5-year OS rates were 94.97% (95% CI 91.57–98.37) and 86.79% (95% CI 81.53–92.06), respectively. Moreover, patients with high median CD1a levels had a significantly lower 5-year OS rate (75.6%) than those with low median CD1a levels (93.5%, p = 0.038). Conclusion: PD-L1, CD1a, and CD83 are variably expressed in triple-negative breast carcinoma tissues, and PD-L1 expression correlates with CD1a and CD83. Higher CD1a levels correlate with PD-L1 expression and predict worse OS in triple-negative breast carcinoma.

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