Effects of Helicobacter suis γ-glutamyl transpeptidase on lymphocytes: modulation by glutamine and glutathione supplementation and outer membrane vesicles as a putative delivery route of the enzyme

Helicobacter (H.) suis colonizes the stomach of the majority of pigs as well as a minority of humans worldwide. Infection causes chronic inflammation in the stomach of the host, however without an effective clearance of the bacteria. Currently, no information is available about possible mechanisms H. suis utilizes to interfere with the host immune response. This study describes the effect on various lymphocytes of the γ-glutamyl transpeptidase (GGT) from H. suis. Compared to whole cell lysate from wild-type H. suis, lysate from a H. suis ggt mutant strain showed a decrease of the capacity to inhibit Jurkat T cell proliferation. Incubation of Jurkat T cells with recombinantly expressed H. suis GGT resulted in an impaired proliferation, and cell death was shown to be involved. A similar but more pronounced inhibitory effect was also seen on primary murine CD4+ T cells, CD8+ T cells, and CD19+ B cells. Supplementation with known GGT substrates was able to modulate the observed effects. Glutamine restored normal proliferation of the cells, whereas supplementation with reduced glutathione strengthened the H. suis GGT-mediated inhibition of proliferation. H. suis GGT treatment abolished secretion of IL-4 and IL-17 by CD4+ T cells, without affecting secretion of IFN-γ. Finally, H. suis outer membrane vesicles (OMV) were identified as a possible delivery route of H. suis GGT to lymphocytes residing in the deeper mucosal layers. Thus far, this study is the first to report that the effects on lymphocytes of this enzyme, not only important for H. suis metabolism but also for that of other Helicobacter species, depend on the degradation of two specific substrates: glutamine and reduced glutatione. This will provide new insights into the pathogenic mechanisms of H. suis infection in particular and infection with gastric helicobacters in general

From the animal house to the field : are there consistent individual differences in immunological profile in wild populations of field voles (Microtus agrestis)?

Inbred mouse strains, living in simple laboratory environments far removed from nature, have been shown to vary consistently in their immune response. However, wildlife populations are typically outbreeding and face a multiplicity of challenges, parasitological and otherwise. In this study we seek evidence of consistent difference in immunological profile amongst individuals in the wild. We apply a novel method in this context, using longitudinal (repeated capture) data from natural populations of field voles, Microtus agrestis, on a range of life history and infection metrics, and on gene expression levels. We focus on three immune genes, IFN-γ, Gata3, and IL-10, representing respectively the Th1, Th2 and regulatory elements of the immune response. Our results show that there was clear evidence of consistent differences between individuals in their typical level of expression of at least one immune gene, and at most all three immune genes, after other measured sources of variation had been taken into account. Furthermore, individuals that responded to changing circumstances by increasing expression levels of Gata3 had a correlated increase in expression levels of IFN-γ. Our work stresses the importance of acknowledging immunological variation amongst individuals in studies of parasitological and infectious disease risk in wildlife populations

Detection, isolation and characterization of Fusobacterium gastrosuis sp. nov. colonizing the stomach of pigs

Nine strains of a novel Fusobacterium sp. were isolated from the stomach of 6-8 months old and adult pigs. The isolates were obligately anaerobic, although they endured 2 hours exposure to air. Phylogenetic analysis based on 16S rRNA and gyrase B genes demonstrated that the isolates showed high sequence similarity with Fusobacterium mortiferum, Fusobacterium ulcerans, Fusobacterium varium, Fusobacterium russii and Fusobacterium necrogenes, but formed a distinct lineage in the genus Fusobacterium. Comparative analysis of the genome of the type strain of this novel Fusobacterium sp. confirmed that it is different from other recognized Fusobacterium spp. DNA-DNA hybridization, fingerprinting and genomic %GC determination further supported the conclusion that the isolates belong to a new, distinct species. The isolates were also distinguishable from these and other Fusobacterium spp. by phenotypical characterization. The strains produced indole and exhibited proline arylamidase and glutamic acid decarboxylase activity. They did not hydrolyse esculin, did not exhibit pyroglutamic acid arylamidase, valine arylamidase, α-galactosidase, β-galactosidase, β-galactosidase-6-phosphate or α-glucosidase activity nor produced acid from cellobiose, glucose, lactose, mannitol, mannose, maltose, raffinose, saccharose, salicin or trehalose. The major fatty acids were C16 : 0 and C18 : 1ω9c. The name Fusobacterium gastrosuis sp. nov. is proposed for the novel isolates with the type strain CDW1(T) (= DSM 101753(T) = LMG 29236(T)). We also demonstrated that Clostridium rectum and Fusobacterium mortiferum represent the same species, with nomenclatural priority for the latter

Helicobacter suis induces changes in gastric inflammation and acid secretion markers in pigs of different ages

International audienceAbstractGastric mRNA expression of markers for acid secretion and inflammation and presence of gastric ulceration was studied in naturally Helicobacter suis-infected and non-infected 2–3 months old, 6–8 months old and adult pigs. In H. suis-infected 2–3 months old pigs, IL-8 and IL-1β transcript levels were upregulated in the pyloric gland zone, indicating an innate immune response. A similar response was demonstrated in the fundic gland zone of adult pigs, potentially due to a shift of H. suis colonization from the pyloric to the fundic gland zone. A Treg response in combination with decreased expressions of IL-8, IL-17A and IFN-γ was indicated to be present in the H. suis-infected 6–8 months old pigs, which may have contributed to persistence of H. suis. In H. suis-infected adult pigs, a Treg response accompanied by a Th17 response was indicated, which may have played a role in the decreased number of H. suis bacteria in the stomach of this age group. The decreased G-cell mass and upregulated expression of somatostatin indicated decreased acid secretion in H. suis-infected 6–8 months old pigs. In H. suis-infected adult pigs, upregulation of most markers for gastric acid secretion and increased G-cell mass was detected. Presence of severe hyperkeratosis and erosions in the non-glandular part of the stomach were mainly seen in the H. suis-positive groups. These results show that H. suis infection affects the expression of markers for acid secretion and inflammation and indicate that these effects differ depending on the infection phase

ALFONSO XIII Y LA INFANTA TERESA SUBIENDO A LA MARQUESINA [Material gráfico]

COPIA DEL MONOGRÁFICO DE LA VISITA DE ALFONSO XIII EN "LA ILUSTRACIÓN HISPANO-AMERICANA". ADQUIRIDA POR EL COLECCIONISTA EN LAS PALMAS G.C. A. CIARÁN, FOTOGRABADOR FIRMA LAS IMÁGENES EN LA PUBLICACIÓN. SIN EMBARGO EL FOTÓGRAFO FUE JAIME MUÑOZ DE BAENAFOTO LLEGADA DE ALFONSO XIII SUBIENDO ESCALERA Y SALUDANDOCopia digital. Madrid : Ministerio de Educación, Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 201

MOESM9 of Helicobacter suis induces changes in gastric inflammation and acid secretion markers in pigs of different ages

Additional file 9. Correlations of altered markers for gastric acid secretion with the number of H. suis bacteria and with the altered markers for inflammation in H. suis -infected pigs of different age groups. r = Pearson correlation coefficient, calculated using SPSS Statistics 24®. A r-value close to 1 indicates a strong, positive correlation, whereas a r-value of −1 indicates a strong, negative correlation. P-values lower than 0.05 are considered to be significant./= no clear correlation, yes = correlation with H. suis colonization rate (see Additional files 6, 8 for the r and p-values)

MOESM8 of Helicobacter suis induces changes in gastric inflammation and acid secretion markers in pigs of different ages

Additional file 8. Overview of important correlations between markers for gastric acid secretion and the number of H. suis bacteria in pigs of different ages. r = Pearson correlation coefficient, calculated using SPSS Statistics 24Ž. A r-value close to 1 indicates a strong, positive correlation, whereas a r-value of -1 indicates a strong, negative correlation. P-values lower than 0.05 are considered to be significant

MOESM3 of Helicobacter suis induces changes in gastric inflammation and acid secretion markers in pigs of different ages

Additional file 3. General overview of the average scores of infiltration with inflammatory cells and lymphoid follicle formation in the fundic and pyloric gland zone of pigs of different ages. Gastritis was scored based on infiltration with inflammatory cells/lymphoid follicle formation, with score 0 = absence of infiltration/absence of lymphoid aggregates, 1 = mild infiltration/small number of lymphoid aggregates (n < 5), 2 = moderate infiltration/large number of lymphoid aggregates (n > 5) or presence of 1 organized lymphoid follicle, 3 = marked infiltration/at least 2 organized lymphoid follicles, n = total number of investigated pigs’ stomachs per age group. The data are shown as the average of the administered scores with standard deviation

MOESM6 of Helicobacter suis induces changes in gastric inflammation and acid secretion markers in pigs of different ages

Additional file 6. Overview of important correlations between markers for inflammation and the number of H. suis bacteria in pigs of different ages. r = Pearson correlation coefficient, calculated using SPSS Statistics 24®. A r-value close to 1 indicates a strong, positive correlation, whereas a r-value of −1 indicates a strong, negative correlation. A p-value lower than 0.05 is considered to be significant