Immunopathological properties of the Campylobacter jejuni flagellins and the adhesin CadF as assessed in a clinical murine infection model

Background: Campylobacter jejuni infections constitute serious threats to human health with increasing prevalences worldwide. Our knowledge regarding the molecular mechanisms underlying host-pathogen interactions is still limited. Our group has established a clinical C. jejuni infection model based on abiotic IL-10-/- mice mimicking key features of human campylobacteriosis. In order to further validate this model for unraveling pathogen-host interactions mounting in acute disease, we here surveyed the immunopathological features of the important C. jejuni virulence factors FlaA and FlaB and the major adhesin CadF (Campylobacter adhesin to fibronectin), which play a role in bacterial motility, protein secretion and adhesion, respectively. Methods and results: Therefore, abiotic IL-10-/- mice were perorally infected with C. jejuni strain 81-176 (WT) or with its isogenic flaA/B (ΔflaA/B) or cadF (ΔcadF) deletion mutants. Cultural analyses revealed that WT and ΔcadF but not ΔflaA/B bacteria stably colonized the stomach, duodenum and ileum, whereas all three strains were present in the colon at comparably high loads on day 6 post-infection. Remarkably, despite high colonic colonization densities, murine infection with the ΔflaA/B strain did not result in overt campylobacteriosis, whereas mice infected with ΔcadF or WT were suffering from acute enterocolitis at day 6 post-infection. These symptoms coincided with pronounced pro-inflammatory immune responses, not only in the intestinal tract, but also in other organs such as the liver and kidneys and were accompanied with systemic inflammatory responses as indicated by increased serum MCP-1 concentrations following C. jejuni ΔcadF or WT, but not ΔflaA/B strain infection. Conclusion: For the first time, our observations revealed that the C. jejuni flagellins A/B, but not adhesion mediated by CadF, are essential for inducing murine campylobacteriosis. Furthermore, the secondary abiotic IL-10-/- infection model has been proven suitable not only for detailed investigations of immunological aspects of campylobacteriosis, but also for differential analyses of the roles of distinct C. jejuni virulence factors in induction and progression of disease

The Cag pathogenicity island and interaction between TLR 2/ NOD 2 and NLRP 3 regulate IL ‐1β production in Helicobacter pylori infected dendritic cells

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/100315/1/eji2723.pd

Analysis of trauma symptomology, trauma-informed care, and student-teacher relationships in a residential treatment center for female adolescents.

Although there is a vast body of literature to support multiple positive outcomes related to positive student-teacher relationships, no prior study has investigated student-teacher relationships within the context of a residential treatment center for abused and neglected adolescents, students who theoretically could benefit from this relationship the most. The first goal of this study was to investigate the effects of student trauma symptomology, teacher beliefs about trauma-informed care, and teachers\u27 emotionally supportive behavior in the classroom on student-teacher relationship quality. Results revealed that teacher beliefs about trauma-informed care and student trauma symptomology, particularly as it is related to \u27Other-Control,\u27 are statistically significant predictor variables of student-teacher relationship quality (F7,45 = 3.002, p = .011, R2 =.318, /).R2 = .212). Additionally, teachers in on-campus schools within residential treatment centers are rarely trained to work with the traumatized students in their classrooms. Therefore, the second goal of this study was to examine the effects of a trauma-informed training intervention for teachers called Risking Connection. Changes in teachers\u27 knowledge about the training material, beliefs about trauma-informed care, and their emotionally supportive behavior in the classroom were evaluated before and after the teacher training as well as the subsequent changes in students\u27 reported trauma symptomology and their perceptions of the student-teacher relationship. Results revealed no statistically significant change in teacher scores; however, this was not expected due to the low sample size of teachers (n = 6). Descriptive statistics suggest that if teacher changes occurred initially, they did not sustain. There was no statistically significant difference in the amount of change in students before and after the teacher training; however, a trend of slightly higher student scores was noted at the third data collection time point directly following the teacher training. Overall, the findings indicate that characteristics of both the students and teachers impact the student-teacher relationship in the residential treatment center setting. Specifically, students\u27 trauma symptomology and teachers\u27 beliefs about the effectiveness of trauma-informed care are predictive of student perceptions of their relationship with their teachers. Implications for research, clinical practice, and effective training for teachers of this population are discussed

Impact of volcanism on the sedimentary record of the Neuquén rift basin, Argentina: towards a cause and effect model

The analysis of volcano-sedimentary infill in sedimentary basins constitutes a challenge for basin analysis and hydrocarbon exploration worldwide. In order to understand the contribution of volcanism to the sedimentary record in rift basins, we study the Jurassic effusive-explosive volcanic infill of an inverted extensional depocentre at the Neuquén Basin, Argentina. A cause and effect model that evaluates the relationship between volcanism and sedimentation was devised to develop a conceptual model for the tectono-stratigraphic evolution of this volcanic rift basin. We show how the variations in the volcanism, coupled with the activity of extensional faults, determined the types of volcanic edifices (i.e., composite volcanoes, graben-calderas, and lava fields). Volcanic edifices controlled the stacking patterns of the volcanic units as well as sedimentary systems. The landform of the volcanic edifices, as well as the styles and scales of the eruptions governed the sedimentary input to the basin, setting the main variables of the sedimentary systems, such as provenance, grain size, transport and deposition and geometry. As a result, the contrasting volcaniclastic input, from higher volcaniclastic input to lower volcaniclastic input, associated with different subsidence patterns, determined the high-resolution syn-rift infill patterns of the extensional depocentre. The cause and effect model presented in this study isolates the variables of the volcanic environments that control the sedimentary scenarios. We suggest that, by adjusting the first order input parameters of the model, these cause and effect scenarios could be adapted to similar rift basins, in order to establish predictive facies models with stratigraphic controls, and the impact of volcanism on their stratigraphic records.Fil: D'Elia, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: Martí, Joan. Consejo Superior de Investigaciones Científicas. Instituto de Ciencias de la Tierra Jaume Almera; EspañaFil: Muravchik, Martin. University Of Bergen; Noruega. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bilmes, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Geología y Paleontología.; ArgentinaFil: Franzese, Juan Rafael. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; Argentin

Site-specific relaxase activity of a VirD2-like protein encoded within the tfs4 genomic island of Helicobacter pylori

Four different type IV secretion systems are variously represented in the genomes of different Helicobacter pylori strains. Two of these, encoded by tfs3 and tfs4 gene clusters are contained within self-transmissible genomic islands. Although chromosomal excision of tfs4 circular intermediates is reported to be dependent upon the function of a tfs4-encoded XerD tyrosine-like recombinase, other factors required for transfer to a recipient cell have not been demonstrated. Here, we characterize the functional activity of a putative tfs4-encoded VirD2-like relaxase protein. Tfs4 VirD2 was purified as a fusion to maltose-binding protein and demonstrated to bind and nick both supercoiled duplex DNA and oligonucleotides in vitro in a manner dependent upon the presence of Mg2+ but independently of any auxiliary proteins. Unusually, concentration-dependent nicking of duplex DNA appeared to require only transient protein-DNA interaction. Although phylogenetically distinct from established relaxase families, site-specific cleavage of oligonucleotides by Tfs4 VirD2 required the nick region sequence 5′-ATCCTG-3′ common to transfer origins (oriT) recognized by MOBP conjugative relaxases. Cleavage resulted in covalent attachment of MBP-VirD2 to the 5′-cleaved end, consistent with conventional relaxase activity. Identification of an oriT-like sequence upstream of tfs4 virD2 and demonstration of VirD2 protein-protein interaction with a putative VirC1 relaxosome component indicate that transfer initiation of the tfs4 genomic island is analogous to mechanisms underlying mobilization of other integrated mobile elements, such as integrating conjugative elements, requiring site-specific targeting of relaxase activity to a cognate oriT sequence

Helicobacter pylori adhesin HopQ engages in a virulence-enhancing interaction with human CEACAMs

Helicobacter pylori specifically colonizes the human gastric epithelium and is the major causative agent for ulcer disease and gastric cancer development. Here, we identify members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family as receptors of H. pylori and show that HopQ is the surface-exposed adhesin that specifically binds human CEACAM1, CEACAM3, CEACAM5 and CEACAM6. HopQ-CEACAM binding is glycan-independent and targeted to the N-domain. H. pylori binding induces CEACAM1-mediated signalling, and the HopQ-CEACAM1 interaction enables translocation of the virulence factor CagA into host cells and enhances the release of pro-inflammatory mediators such as interleukin-8. Based on the crystal structure of HopQ, we found that a beta-hairpin insertion (HopQ-ID) in HopQ's extracellular 3+4 helix bundle domain is important for CEACAM binding. A peptide derived from this domain competitively inhibits HopQ-mediated activation of the Cag virulence pathway, as genetic or antibody-mediated abrogation of the HopQ function shows. Together, our data suggest the HopQ-CEACAM1 interaction to be a potentially promising novel therapeutic target to combat H. pylori-associated diseases.</p

Molecular mechanisms of gastric epithelial cell adhesion and injection of CagA by Helicobacter pylori

Helicobacter pylori is a highly successful pathogen uniquely adapted to colonize humans. Gastric infections with this bacterium can induce pathology ranging from chronic gastritis and peptic ulcers to gastric cancer. More virulent H. pylori isolates harbour numerous well-known adhesins (BabA/B, SabA, AlpA/B, OipA and HopZ) and the cag (cytotoxin-associated genes) pathogenicity island encoding a type IV secretion system (T4SS). The adhesins establish tight bacterial contact with host target cells and the T4SS represents a needle-like pilus device for the delivery of effector proteins into host target cells such as CagA. BabA and SabA bind to blood group antigen and sialylated proteins respectively, and a series of T4SS components including CagI, CagL, CagY and CagA have been shown to target the integrin β1 receptor followed by injection of CagA across the host cell membrane. The interaction of CagA with membrane-anchored phosphatidylserine may also play a role in the delivery process. While substantial progress has been made in our current understanding of many of the above factors, the host cell receptors for OipA, HopZ and AlpA/B during infection are still unknown. Here we review the recent progress in characterizing the interactions of the various adhesins and structural T4SS proteins with host cell factors. The contribution of these interactions to H. pylori colonization and pathogenesis is discussed