Delineation of the Innate and Adaptive T-Cell Immune Outcome in the Human Host in Response to Campylobacter jejuni Infection

Background: Campylobacter jejuni is the most prevalent cause of bacterial gastroenteritis worldwide. Despite the significant health burden this infection presents, molecular understanding of C. jejuni-mediated disease pathogenesis remains poorly defined. Here, we report the characterisation of the early, innate immune response to C. jejuni using an ex-vivo human gut model of infection. Secondly, impact of bacterial-driven dendritic cell activation on T-cell mediated immunity was also sought.Methodology: Healthy, control paediatric terminal ileum or colonic biopsy tissue was infected with C. jejuni for 8-12 hours. Bacterial colonisation was followed by confocal microscopy and mucosal innate immune responses measured by ELISA. Marked induction of IFN gamma with modest increase in IL-22 and IL-17A was noted. Increased mucosal IL-12, IL-23, IL-1 beta and IL-6 were indicative of a cytokine milieu that may modulate subsequent T-cell mediated immunity. C. jejuni-driven human monocyte-derived dendritic cell activation was followed by analyses of T cell immune responses utilising flow cytometry and ELISA. Significant increase in Th-17, Th-1 and Th-17/Th-1 double-positive cells and corresponding cytokines was observed. The ability of IFN gamma, IL-22 and IL-17 cytokines to exert host defence via modulation of C. jejuni adhesion and invasion to intestinal epithelia was measured by standard gentamicin protection assay.Conclusions: Both innate and adaptive T cell-immunity to C. jejuni infection led to the release of IFN gamma, IL-22 and IL-17A; suggesting a critical role for this cytokine triad in establishing host anti-microbial immunity during the acute and effectors phase of infection. In addition, to their known anti-microbial functions; IL-17A and IL-17F reduced the number of intracellular C. jejuni in intestinal epithelia, highlighting a novel aspect of how IL-17 family members may contribute to protective immunity against C. jejuni

Swimming speed alteration of larvae of Balanus amphitrite as a behavioural end-point for laboratory toxicological bioassays

n this study, we investigate the feasibility of developing a new behavioural toxicity bioassay (Swimming Speed Alteration test-SSA test) with larvae of Balanus amphitrite (Crustacea Cirripedia). This organism was chosen as a model for different reasons: it is present all over the world, simple to be reared, easily available, and also because barnacles play an important role in the coastal ecosystem. In addition, all the operations related to the rearing and test execution are comparatively cheap. This bioassay was performed with several classes of chemical pollutants (antifouling biocides, neurotoxic pesticides, and heavy metals) and with environmental samples (sediment elutriates). The measurement of swimming speed, by means of video-graphic techniques, proved to be a valid instrument in highlighting the sub-lethal levels of toxicity caused by the different tested samples. In conclusion, the SSA test is able to provide in a biomonitoring program a good behavioural integrated output, which is also repeatable, sensitive, easily interpretable, and truly representative of a broad range of toxic compounds and environmental toxic matrices which are, generally, very complex and difficult to analyse. For all of these reasons, it could be proposed as a non-specific behavioural end-point

Dense genotyping of immune-related disease regions identifies 14 new susceptibility loci for juvenile idiopathic arthritis

Analysis of the ImmunoChip single nucleotide polymorphism (SNP) array in 2816 individuals, comprising the most common subtypes (oligoarticular and RF negative polyarticular) of juvenile idiopathic arthritis (JIA) and 13056 controls strengthens the evidence for association to three known JIA-risk loci (HLA, PTPN22 and PTPN2) and has identified fourteen risk loci reaching genome-wide significance (p < 5 × 10(-8)) for the first time. Eleven additional novel regions showed suggestive evidence for association with JIA (p < 1 × 10(-6)). Dense-mapping of loci along with bioinformatic analysis has refined the association to one gene for eight regions, highlighting crucial pathways, including the IL-2 pathway, in JIA disease pathogenesis. The entire ImmunoChip loci, HLA region and the top 27 loci (p < 1 × 10(-6)) explain an estimated 18%, 13% and 6% risk of JIA, respectively. Analysis of the ImmunoChip dataset, the largest cohort of JIA cases investigated to date, provides new insight in understanding the genetic basis for this childhood autoimmune disease