The Microenvironment of Visceral Adipose Tissue and Liver Alter Natural Killer Cell Viability and Function

The role of NK cells in visceral adipose tissue (VAT) and liver inflammation in obesity is not fully understood. This study investigated the frequency, cytokine expression, chemokine receptor, and cytotoxicity receptor profile of NK cells in the blood, omentum, and liver of patients with the obesity-associated cancer, oesophageal adenocarcinoma (OAC). The effect of chronically inflamed tissue microenvironments on NK cell viability and function was also examined. We identified significantly lower NK cell frequencies in the liver of OAC patients compared with healthy controls and within the omentum and liver of OAC patients compared with blood, whereas IL-10-producing populations were significantly higher. Interestingly, our data suggest that reduced frequencies of NK cells in omentum and liver of OAC patients are not a result of impaired NK cell chemotaxis to these tissues. In fact, our functional data revealed that secreted factors from omentum and liver of OAC patients induce significant levels of NK cell death and lead to reduced percentages of TNF-α+ and NKP46+ NK cells and higher frequencies of IL-10-producing NK cells. Together, these data suggest that the omental and hepatic microenvironments of OAC patients alter the NK cell phenotype to a more anti-inflammatory homeostatic role

A variant in the CD209 promoter is associated with the severity of liver disease in chronic Hepatitis C virus infection

CD209, a c-type lectin expressed by dendritic cells (DCs) acts as a pathogen recognition receptor. A single nucleotide polymorphism (SNP) in the promoter region of CD209 (-336 A/G; rs4804803) affects transcription and is associated with the severity of Tuberculosis and Dengue fever. As CD209 binds Hepatitis C Virus (HCV) glycoprotein-E2, we investigated this SNP in the context of chronic HCV infection. 131 Irish women who had received HCV contaminated Anti-D immunoglobulin and 79 healthy controls were genotyped. We found no association between rs4804803 and the risk of HCV chronicity. However, of those with chronic infection, possession of at least one g-allele was associated with more advanced liver disease, with significantly higher liver fibrosis scores and levels of alanine transaminase (ALT) observed. We conclude that rs4804803, a SNP in the CD209 promoter contributes to the severity of liver disease in chronic HCV infection

Just how inflamed is the normal gut?

Comment on Spontaneous secretion of interferon gamma and interleukin 4 by human intraepithelial and lamina propria gut lymphocytes

Humoral response to alpha gliadin as serological screening test for coeliac disease.

The diagnostic value of measuring alpha gliadin antibodies in children with suspected coeliac disease has been evaluated prospectively. Jejunal biopsy and alpha gliadin antibody measurements were performed in 77 consecutive children who were being investigated for a suspected malabsorption syndrome. The typical small intestinal histological lesion of coeliac disease was found, and this diagnosis was subsequently confirmed clinically in 20 children. Raised IgG alpha gliadin antibody concentrations were found in 19 (95%). Fifty of 57 patients (88%) with a normal jejunal mucosa had normal alpha gliadin antibody concentrations. These results are similar to those previously reported in a prospective study of adult patients with coeliac disease and indicate that measurement of alpha gliadin antibody is a highly sensitive and specific screening test for childhood coeliac diseas

Innate immune gene expression differentiates the early avian intestinal response between Salmonella and Campylobacter

Salmonella enterica serovar Typhimurium and Campylobacter jejuni are major human pathogens, yet colonise chickens without causing pathology. The aim of this study was to compare intestinal innate immune responses to both bacterial species, in a 4-week-old broiler chicken model. Challenged and control birds were sacrificed and tissue samples taken for histopathology and RNA extraction. No significant clinical or pathological changes were observed in response to infection with either bacterial species. Expression of selected genes involved in pathogen detection and the innate immune response were profiled in caecal tissues by quantitative real-time PCR. TLR4 and TLR21 gene expression was transiently increased in response to both bacterial species (P < 0.05). Significant increases in TLR5 and TLR15 gene expression were detected in response to S. Typhimurium but not to C. jejuni. Transient increases of proinflammatory cytokine (IL6 and IFNG) and chemokine (IL8 and K60) genes increased as early as 6 h in response to S. Typhimurium. Minimal cytokine gene expression was detected in response to C. jejuni after 20 h. IL8 gene expression however, was significantly increased by 24-fold (P < 0.01). The differential expression profiles of innate immune genes in both infection models shed light on the tailored responses of the host immune system to specific microbes. It is further evidence that innate regulation of these responses is an important prerequisite to preventing development of disease

Alpha gliadin antibody levels: a serological test for coeliac disease.

The diagnostic value in coeliac disease of circulating antibodies to casein, crude gliadin, and alpha gliadin was assessed using an adaption of the enzyme linked immunosorbent assay system. alpha Gliadin was the only antigen which consistently separated 26 patients with untreated coeliac disease from 26 normal controls and 13 patients with chronic inflammatory bowel disease. The mean assay index for the 26 patients was 3.1 (SD 1.2) compared with 1.05 (0.5) for the normal controls and 1.1 (0.6) for patients with chronic inflammatory bowel disease. The alpha gliadin antibody levels of six patients with coeliac disease who had maintained a gluten free diet for at least two years were not significantly higher than normal (1.0 (0.4)). The validity of the test was determined in 90 consecutive patients who were being investigated for the presence of coeliac disease. Levels of alpha gliadin antibody were raised in 36 out of 44 patients found to have histologically proved coeliac disease and in six out of 46 subjects whose jejunal mucosa was normal. Serial alpha gliadin concentrations were measured in 12 patients with coeliac disease who had repeat jejunal biopsies performed six months after starting a gluten free diet. The levels of antibody fell in seven of the eight patients whose jejunal mucosa improved on maintaining the diet. They remained raised in four patients who did not adhere to the diet and whose mucosa did not improve. Although a test measuring alpha gliadin antibodies is unlikely to replace jejunal biopsy in the diagnosis of coeliac disease it may be useful in screening for the disease among outpatient

Gliadin antibody detection in gluten enteropathy.

Circulating antigliadin antibody has been described in patients with gluten enteropathy although the prevalence varies in different studies. It has been suggested that the investigation for antigliadin antibody might be useful as a screening test. The object of the present study was to evaluate two different techniques for assaying these antibodies ? an indirect immunofluorescent method and an enzyme-linked immunosorbent assay (ELISA). Antibodies were assayed in the sera of 102 patients in whom jejunal biopsies were also obtained. The specificity of both tests was greater than 95%, and the correlation between the presence of antibody and histology was significant (p < 0.005), though the sensitivity of each test was less than 70

Increased concanavalin A induced suppression in treated and untreated coeliac disease.

The generation of suppression by concanavalin A in peripheral blood mononuclear cells in treated and untreated coeliac subjects using an in vitro assay was found to be significantly increased when compared with controls. The response of peripheral blood mononuclear cells to the plant mitogen concanavalin A (con A) was also significantly depressed in both groups of coeliac patients. It is proposed that the depressed cell mediated immunity found in this and other studies in coeliac patients is because of increased suppression. The possible connection between these findings and the increased incidence of malignancy also found in coeliac disease is discussed

Bovine b946;-defensin gene family: Opportunities to improve animal health?

Recent analysis of the bovine genome revealed an expanded suite of ?-defensin genes that encode what are referred to as antimicrobial or host defense peptides (HDPs). Whereas primate genomes also encode ?- and ?-defensins, the bovine genome contains only the ?-defensin subfamily of HDPs. ?-Defensins perform diverse functions that are critical to protection against pathogens but also in regulation of the immune response and reproduction. As the most comprehensively studied subclass of HDPs, ?-defensins possess the widest taxonomic distribution, found in invertebrates as well as plants, indicating an ancient point of origin. Cross-species comparison of the genomic arrangement of ?-defensin gene repertoire revealed them to vary in number among species presumably due to differences in pathogenic selective pressures but also genetic drift. ?-Defensin genes exist in a single cluster in birds, but four gene clusters exist in dog, rat, mouse, and cow. In humans and chimpanzees, one of these clusters is split in two as a result of a primate-specific pericentric inversion producing five gene clusters. A cluster of ?-defensin genes on bovine chromosome 13 has been recently characterized, and full genome sequencing has identified extensive gene copy number variation on chromosome 27. As a result, cattle have the most diverse repertoire of ?-defensin genes so far identified, where four clusters contain at least 57 genes. This expansion of ?-defensin HDPs may hold significant potential for combating infectious diseases and provides opportunities to harness their immunological and reproductive functions in commercial cattle populations