scholarly journals Chlamydia suis is associated with intestinal NF-κB activation in experimentally infected gnotobiotic piglets

2020 ◽  
Vol 78 (6) ◽  
Author(s):  
Helen Aumayer ◽  
Cory Ann Leonard ◽  
Theresa Pesch ◽  
Barbara Prähauser ◽  
Sabina Wunderlin ◽  
...  
Keyword(s):  
Lamina Propria ◽  
Intestinal Epithelium ◽  
Immune Cell ◽  
Clinical Symptoms ◽  
Recovery Phase ◽  
Early Event ◽  
Post Inoculation ◽  
Single Animal ◽  
Chlamydia Suis ◽  
Gnotobiotic Piglets

ABSTRACT Chlamydia suis intestinal infection of single-animal experimental groups of gnotobiotic newborn piglets was previously reported to cause severe, temporary small intestinal epithelium damage. We investigated archived intestinal samples for pro-inflammatory nuclear factor kappa B (NF-κB) activation, Interleukin (IL)-6 and IL-8 production and immune cell influx. Samples were collected 2, 4 and 7 days post-inoculation with C. suis strain S45/6 or mock inoculum (control). Increased nuclear localization of epithelial NF-κB, representative of activation, in the jejunum and ileum of C. suis-infected animals, compared to uninfected controls, began by 2 days post-infection (dpi) and persisted through 7 dpi. Infected animals showed increased production of IL-8, peaking at 2 dpi, compared to controls. Infection-mediated CD45-positive immune cell influx into the jejunal lamina propria peaked at 7 dpi, when epithelial damage was largely resolved. Activation of NF-κB appears to be a key early event in the innate response of the unprimed porcine immune system challenged with C. suis. This results in an acute phase, coinciding with the most severe clinical symptoms, diarrhea and weight loss. Immune cells recruited shortly after infection remain present in the lamina propria during the recovery phase, which is characterized by reduced chlamydial shedding and restored intestinal epithelium integrity.

scholarly journals Circulating miRNAs Related to Epithelial–Mesenchymal Transitions (EMT) as the New Molecular Markers in Endometriosis

2021 ◽  
Vol 43 (2) ◽  
pp. 900-916
Author(s):  
Anna Zubrzycka ◽  
Monika Migdalska-Sęk ◽  
Sławomir Jędrzejczyk ◽  
Ewa Brzeziańska-Lasota
Keyword(s):  
Molecular Mechanisms ◽  
Immune Cell ◽  
Epithelial Mesenchymal Transition ◽  
Clinical Symptoms ◽  
Diagnostic Tools ◽  
Endometrial Stromal Cells ◽  
Disease Etiology ◽  
Diagnostic Biomarkers ◽  
Mesenchymal Transition ◽  
Non Invasive

Endometriosis is a chronic gynecological disease defined by the presence of endometrial-like tissue found outside the uterus, most commonly in the peritoneal cavity. Endometriosis lesions are heterogenous but usually contain endometrial stromal cells and epithelial glands, immune cell infiltrates and are vascularized and innervated by nerves. The complex etiopathogenesis and heterogenity of the clinical symptoms, as well as the lack of a specific non-invasive diagnostic biomarkers, underline the need for more advanced diagnostic tools. Unfortunately, the contribution of environmental, hormonal and immunological factors in the disease etiology is insufficient, and the contribution of genetic/epigenetic factors is still fragmentary. Therefore, there is a need for more focused study on the molecular mechanisms of endometriosis and non-invasive diagnostic monitoring systems. MicroRNAs (miRNAs) demonstrate high stability and tissue specificity and play a significant role in modulating a range of molecular pathways, and hence may be suitable diagnostic biomarkers for the origin and development of endometriosis. Of these, the most frequently studied are those related to endometriosis, including those involved in epithelial–mesenchymal transition (EMT), whose expression is altered in plasma or endometriotic lesion biopsies; however, the results are ambiguous. Specific miRNAs expressed in endometriosis may serve as diagnostics markers with prognostic value, and they have been proposed as molecular targets for treatment. The aim of this review is to present selected miRNAs associated with EMT known to have experimentally confirmed significance, and discuss their utility as biomarkers in endometriosis.

scholarly journals Significance of nucleic acid positive anal swab in COVID-19 patients

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 332-337
Author(s):  
Xiaoli Li ◽  
Lei Rong ◽  
Peiyan Zhang ◽  
Jian Xu ◽  
Yan Rong
Keyword(s):  
Platelet Count ◽  
Clinical Symptoms ◽  
Influence Factors ◽  
Recovery Phase ◽  
Negative Group ◽  
Pharyngeal Swab ◽  
Positive Group ◽  
Oral Transmission ◽  
Significant Difference ◽  
Anal Swab

Abstract Aim We compared the clinical characteristics of patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) positive and negative anal swabs during coronavirus disease 2019 (COVID-19) recovery and investigated the clinical significance and influence factors of anal swab detection. Methods This study retrospectively analyzed 23 moderate COVID-19 patients in the recovery phase. They were divided into anal swab positive group (n = 13) (negative for pharyngeal swabs but positive for anal swabs) and anal swab negative group (n = 10) (negative for pharyngeal and anal swabs). The epidemiology, clinical symptoms, time of pharyngeal swabs turning negative, and laboratory results were compared. Results The time of pharyngeal swabs turning negative in the anal swab positive group was 6 (5–8.5) days, significantly longer than that in the anal swab negative group (1 (1–4.25) days), P = 0.0002). The platelet count of the anal swab positive group was significantly lower than that of the anal swab negative group (198 (135–235) × 109/L vs 240.5 (227–264.75) × 109/L, P = 0.0248). No significant difference was observed between the two groups in other variables. Conclusions The time of pharyngeal swab turning negative in anal swab positive patients is longer than that in anal swab negative patients. The platelet count can be used as an indicator for viral infection evaluation. For patients with a longer time of pharyngeal swabs turning negative, the combined testing of the anal swab and platelet counts may help to avoid pharyngeal swab false negatives, premature discharge, and the possibility of fecal-oral transmission.

scholarly journals Cdx2 regulates immune cell infiltration in the intestine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Simon Chewchuk ◽  
Sanzida Jahan ◽  
David Lohnes
Keyword(s):  
Intestinal Epithelium ◽  
Target Genes ◽  
Immune Cell ◽  
Cell Number ◽  
Macrophage Infiltration ◽  
Intestinal Homeostasis ◽  
Chronic Inflammatory Response ◽  
Complex Protein ◽  
Inflammatory Phenotype

AbstractThe intestinal epithelium is a unique tissue, serving both as a barrier against pathogens and to conduct the end digestion and adsorption of nutrients. As regards the former, the intestinal epithelium contains a diverse repertoire of immune cells, including a variety of resident lymphocytes, macrophages and dendritic cells. These cells serve a number of roles including mitigation of infection and to stimulate regeneration in response to damage. The transcription factor Cdx2, and to a lesser extent Cdx1, plays essential roles in intestinal homeostasis, and acts as a context-dependent tumour suppressor in colorectal cancer. Deletion of Cdx2 from the murine intestinal epithelium leads to macrophage infiltration resulting in a chronic inflammatory response. However the mechanisms by which Cdx2 loss evokes this response are poorly understood. To better understand this relationship, we used a conditional mouse model lacking all intestinal Cdx function to identify potential target genes which may contribute to this inflammatory phenotype. One such candidate encodes the histocompatability complex protein H2-T3, which functions to regulate intestinal iCD8α lymphocyte activity. We found that Cdx2 occupies the H3-T3 promoter in vivo and directly regulates its expression via a Cdx response element. Loss of Cdx function leads to a rapid and pronounced attenuation of H2-T3, followed by a decrease in iCD8α cell number, an increase in macrophage infiltration and activation of pro-inflammatory cascades. These findings suggest a previously unrecognized role for Cdx in intestinal homeostasis through H2-T3-dependent regulation of iCD8α cells.

scholarly journals Monocyte-induced recovery of inflammation-associated hepatocellular dysfunction in a biochip-based human liver model

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Marko Gröger ◽  
Knut Rennert ◽  
Benjamin Giszas ◽  
Elisabeth Weiß ◽  
Julia Dinger ◽  
...  
Keyword(s):  
Liver Dysfunction ◽  
Human Liver ◽  
Immune Cell ◽  
Early Event ◽  
Liver Sinusoid ◽  
Human Sepsis ◽  
Cellular Events ◽  
Cell Layers ◽  
Parenchymal Cells

Abstract Liver dysfunction is an early event in sepsis-related multi-organ failure. We here report the establishment and characterization of a microfluidically supported in vitro organoid model of the human liver sinusoid. The liver organoid is composed of vascular and hepatocyte cell layers integrating non-parenchymal cells closely reflecting tissue architecture and enables physiological cross-communication in a bio-inspired fashion. Inflammation-associated liver dysfunction was mimicked by stimulation with various agonists of toll-like receptors. TLR-stimulation induced the release of pro- and anti-inflammatory cytokines and diminished expression of endothelial VE-cadherin, hepatic MRP-2 transporter and apolipoprotein B (ApoB), resulting in an inflammation-related endothelial barrier disruption and hepatocellular dysfunction in the liver organoid. However, interaction of the liver organoid with human monocytes attenuated inflammation-related cell responses and restored MRP-2 transporter activity, ApoB expression and albumin/urea production. The cellular events observed in the liver organoid closely resembled pathophysiological responses in the well-established sepsis model of peritoneal contamination and infection (PCI) in mice and clinical observations in human sepsis. We therefore conclude that this human liver organoid model is a valuable tool to investigate sepsis-related liver dysfunction and subsequent immune cell-related tissue repair/remodeling processes.

scholarly journals The Causes and Long-Term Consequences of Viral Encephalitis

2021 ◽  
Vol 15 ◽  
Author(s):  
Karen Bohmwald ◽  
Catalina A. Andrade ◽  
Nicolás M. S. Gálvez ◽  
Valentina P. Mora ◽  
José T. Muñoz ◽  
...  
Keyword(s):  
Viral Encephalitis ◽  
Viral Infections ◽  
Immune Cell ◽  
Clinical Symptoms ◽  
Brain Inflammation ◽  
High Morbidity ◽  
Stiff Neck ◽  
The Impact ◽  
The Brain

Reports regarding brain inflammation, known as encephalitis, have shown an increasing frequency during the past years. Encephalitis is a relevant concern to public health due to its high morbidity and mortality. Infectious or autoimmune diseases are the most common cause of encephalitis. The clinical symptoms of this pathology can vary depending on the brain zone affected, with mild ones such as fever, headache, confusion, and stiff neck, or severe ones, such as seizures, weakness, hallucinations, and coma, among others. Encephalitis can affect individuals of all ages, but it is frequently observed in pediatric and elderly populations, and the most common causes are viral infections. Several viral agents have been described to induce encephalitis, such as arboviruses, rhabdoviruses, enteroviruses, herpesviruses, retroviruses, orthomyxoviruses, orthopneumovirus, and coronaviruses, among others. Once a neurotropic virus reaches the brain parenchyma, the resident cells such as neurons, astrocytes, and microglia, can be infected, promoting the secretion of pro-inflammatory molecules and the subsequent immune cell infiltration that leads to brain damage. After resolving the viral infection, the local immune response can remain active, contributing to long-term neuropsychiatric disorders, neurocognitive impairment, and degenerative diseases. In this article, we will discuss how viruses can reach the brain, the impact of viral encephalitis on brain function, and we will focus especially on the neurocognitive sequelae reported even after viral clearance.

Balancing Precision vs. Cohort Transcriptomic Analysis of Acute and Recovery Phase of Viral Bronchiolitis

2021 ◽  
Author(s):  
Ruchir Gupta ◽  
Mara L Leimanis ◽  
Marie Adams ◽  
Andre S Bachmann ◽  
Katie L. Uhl ◽  
...  
Keyword(s):  
Cell Activation ◽  
Viral Infections ◽  
Immune Cell ◽  
Healthcare Delivery ◽  
Recovery Phase ◽  
Adverse Outcomes ◽  
Cytokine Signaling ◽  
Cytokine Activation ◽  
Biological Responses ◽  
Syncytial Virus

Viral infections affecting the lower respiratory tract place enormous burdens on hospitals. As neither vaccines nor anti-viral agents exist for many viruses, understanding risk factors and outcomes in each patient using minimally invasive analysis, such as blood, can lead to improved healthcare delivery. A cohort of PAXGene RNAseq of infants admitted with moderate or severe acute bronchiolitis and respiratory syncytial virus (RSV) were compared with case-control statistical analysis and cohort-based outlier mapping for precision transcriptomics. Severe bronchiolitis patients had signatures connected to the immune system, interferon signaling, and cytokine signaling, with marked sex differences in XIST, RPS4Y1, KDM5D, and LINC00278 for severity. Several patients had unique secondary infections, cytokine activation, immune responses, biological pathways, and immune cell activation, highlighting the need for defining patient-level transcriptomic signatures. Balancing relative contributions of cohort-based biomarker discoveries with patient's biological responses is needed to understand totality of mechanisms of adverse outcomes in viral bronchiolitis.

scholarly journals P073 Compartmentalised human gut immunity: studies of innate and adaptive lymphocyte distribution in the epithelium, lamina propria and GALT of healthy gut mucosa by flow cytometry

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S172-S172
Author(s):  
A Carrasco Garcia ◽  
A Rao ◽  
E Kokkinou ◽  
S Haapaniemi ◽  
U Lindforss ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cell ◽  
Lamina Propria ◽  
Immune Cell ◽  
Cd8 T Cell ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Human Gut ◽  
Cell Ratio ◽  
Health And Disease

Abstract Background The human gut mucosal immune system is compartmentalised in distinct and specialised immune niches. The epithelium and the lamina propria have been proposed as effector sites, while gut-associated lymphoid tissues (GALTs) constitute inductive immune niches. The major mucosal GALTs are the Peyer’s patches in the ileum and the colonic isolated lymphoid follicles (ILFs), scattered in the submucosa of the colon. The majority of studies of human gut immune function in health and disease have analysed unfractionated mucosal tissue samples. Hence, in contrast to mice, little is known about compartmentalised immune cell specialisation in the human gut. The aim of this study was to use novel dissection methods to analyse separate human gut immune niches. Methods Macroscopically healthy margins from colorectal cancer colectomies were obtained at a minimum distance of 10 cm from the tumour border. After faeces, mucus, fat and muscle removal, Peyer’s patches were identified and dissected using a stereomicroscope (based on Keita et al., Lab Invest, 2006). Colonic mucosa and submucosa (containing ILFs) fractions were mechanically separated by forceps (based on the method developed by Fenton et al., Immunity, under revision). Isolation of epithelial and lamina propria fractions from the mucosal compartment was performed by calcium chelation (DTT and EDTA) and enzymatic digestion (Collagenase II and DNAse), respectively. Cell suspensions from each fraction were analysed by flow cytometry (BD LSR-Fortessa and BD FACSymphony). Results As expected, mucosal GALTs were characterised by an enrichment of germinal centre B cells (CD19+CD20+CD38+), lymphoid tissue-like innate lymphoid cells (Lin−CD127+CD117+Nrp1+) and a higher CD4+/CD8+ T-cell ratio vs. mucosa, whereas the mucosal fraction was enriched for plasma cells (CD19+CD20−CD38high) and distinguished by a decreased CD4+/CD8+ T-cell ratio as compared with the GALT in both ileum and colon. CD19+/CD3+ ratios were only higher in Peyer’s patches but not in colonic submucosa enriched with ILFs, possibly due to the smaller size of the B-cell follicles in the latter. The intraepithelial compartment lacked B cells and contained more γδ-T cells as compared with the GALT and lamina propria. Conclusion We have used novel dissection methods in human intestinal tissues that reveal a compartmentalised immune cell specialisation that is in line with what has previously been described in mice. The method will allow for future deeper analysis of the human gut immune niches in health and disease, such as in inflammatory bowel disease.

Effect of loading practices and 6-hour road transport on the physiological responses of yearling cattle

2008 ◽  
Vol 48 (7) ◽  
pp. 1028 ◽  
Author(s):  
S. G. Pettiford ◽  
D. M. Ferguson ◽  
J. M. Lea ◽  
C. Lee ◽  
D. R. Paull ◽  
...  
Keyword(s):  
Plasma Cortisol ◽  
Acute Phase Protein ◽  
Physiological Responses ◽  
Road Transport ◽  
Recovery Phase ◽  
Controlled Study ◽  
Blood Samples ◽  
Single Animal ◽  
Phase Protein ◽  
Rate Of Recovery

A controlled study using 16 yearling Angus steers was conducted to determine the physiological responses associated with loading practices followed by 6 h of road transport and 17 h of post-transport recovery. The cattle were quietly mustered from grazing at pasture and directly loaded onto a truck for transport. During loading, cattle received either four consecutive prods with a commercial electric prodder (n = 8) or no prodding (control, n = 8). The experiment was performed in four replicates, conducted on consecutive days, with four animals (n = 2 per treatment) utilised on each day. On the truck, cattle were confined to pens that each held a single animal facing the direction of travel. Blood samples were taken via jugular catheters before and during the 6 h journey and during the 17 h recovery phase. Samples were analysed for haematology, osmolality and plasma cortisol, total protein, creatine kinase, blood urea nitrogen and the acute phase protein haptoglobin. The physiological measurements indicated that most stress occurred during loading and the initial stages of transport, but after this, the cattle habituated and were able to cope with the 6 h of transport. After 17 h of recovery, nearly all the variables measured had returned to their pre-transport levels. Use of an electric prodder during loading did not modify the physiological responses to loading, transport or the rate of recovery compared with the controls.

scholarly journals Broad Up-Regulation of Innate Defense Factors during Acute Cholera

2007 ◽  
Vol 75 (5) ◽  
pp. 2343-2350 ◽  
Author(s):  
Carl-Fredrik Flach ◽  
Firdausi Qadri ◽  
Taufiqur R. Bhuiyan ◽  
Nur H. Alam ◽  
Eva Jennische ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Lamina Propria ◽  
Intestinal Epithelium ◽  
Defense Mechanisms ◽  
Expression Patterns ◽  
Immunohistochemical Analysis ◽  
Duodenal Mucosa ◽  
Innate Defense ◽  
Microarray Screening

ABSTRACT We used a whole-genome microarray screening system (Affymetrix human GeneChips covering 47,000 different transcripts) to examine the gene expression in duodenal mucosa during acute cholera. Biopsies were taken from the duodenal mucosa of seven cholera patients 2 and 30 days after the onset of diarrhea, and the gene expression patterns in the acute- and convalescent-phase samples were compared pairwise. Of about 21,000 transcripts expressed in the intestinal epithelium, 29 were defined as transcripts that were up-regulated and 33 were defined as transcripts that were down-regulated during acute cholera. The majority of the up-regulated genes characterized were found to have an established or possible role in the innate defense against infections; these genes included the LPLUNC1, LF, VCC1, TCN1, CD55, SERPINA3, MMP1, MMP3, IL1B, LCN2, SOCS3, GDF15, SLPI, CXCL13, and MUC1 genes. The results of confirmative PCR correlated well with the microarray data. An immunohistochemical analysis revealed increased expression of lactoferrin in lamina propria cells and increased expression of CD55 in epithelial cells, whereas increased expression of the SERPINA3 protein (α1-antichymotrypsin) was detected in both lamina propria and epithelial cells during acute cholera. The expression pattern of CD55 and SERPINA3 in cholera toxin (CT)-stimulated Caco-2 cells was the same as the pattern found in the intestinal mucosa during acute cholera, indicating that the activation of the CD55 and SERPINA3 genes in intestinal epithelium was induced by CT. In conclusion, during acute cholera infection, innate defense mechanisms are switched on to an extent not described previously. Both direct effects of CT on the epithelial cells and changes in the lamina propria cells contribute to this up-regulation.

scholarly journals Hypophosphatemia as Unusual Cause of ARDS in Cushing’s Syndrome Secondary to Ectopic CRH Production. A Case Report

2008 ◽  
Vol 8 ◽  
pp. 138-144 ◽  
Author(s):  
Stefania Mondello ◽  
Vincenzo Fodale ◽  
Salvatore Cannav ◽  
Carmela Aloisi ◽  
Barbara Almoto ◽  
...  
Keyword(s):  
Case Report ◽  
Cushing’S Syndrome ◽  
Clinical Symptoms ◽  
Laboratory Data ◽  
Blood Gases ◽  
Recovery Phase ◽  
Cushing's Syndrome ◽  
Surgical Removal ◽  
Arterial Blood ◽  
Underlying Disorder

Hypophosphatemia is an unusual cause of acute respiratory distress syndrome (ARDS). We describe a hypophosphatemia-related ARDS case report of a 50-year-old woman with ACTH dependent Cushing's syndrome secondary to ectopic CRH production. The patient clinically showed hypotension tachypnea and increasing dyspnea. Laboratory data showed carbohydrate intolerance, severe hypokalemia, and hypophosphatemia. Arterial blood gases measurement revealed hypocapnia and elevation in bicarbonate values. Chest X-ray showed diffuse bilateral alveolar infiltrates similar to acute pulmonary edema and Kerley's striae. Chest CT scan evidenced diffuse ground glass opacification, bilateral patchy consolidation, and fibrosis, compatible with the recovery phase of ARDS. Clinical symptoms and laboratory examinations supported the diagnosis of ARDS. The patient was managed with supplemental potassium, octreotide, and oxygen therapy. Hypophosphatemia was managed by treating the underlying disorder. Successive surgical removal of the adrenal gland led to complete resolution of Cushing's syndrome. In conclusion, although rare and associated with specific risk factors, hypophosphatemia should be suspected in patients who develop unexplained ARDS.

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