Expression and Putative Function of Innate Immunity Genes under in situ Conditions in the Symbiotic Hydrothermal Vent Tubeworm Ridgeia piscesae

The relationships between hydrothermal vent tubeworms and sulfide-oxidizing bacteria have served as model associations for understanding chemoautotrophy and endosymbiosis. Numerous studies have focused on the physiological and biochemical adaptations that enable these symbioses to sustain some of the highest recorded carbon fixation rates ever measured. However, far fewer studies have explored the molecular mechanisms underlying the regulation of host and symbiont interactions, specifically those mediated by the innate immune system of the host. To that end, we conducted a series of studies where we maintained the tubeworm, Ridgeia piscesae, in high-pressure aquaria and examined global and quantitative changes in gene expression via high-throughput transcriptomics and quantitative real-time PCR (qPCR). We analyzed over 32,000 full-length expressed sequence tags as well as 26 Mb of transcript sequences from the trophosome (the organ that houses the endosymbiotic bacteria) and the plume (the gas exchange organ in contact with the free-living microbial community). R. piscesae maintained under conditions that promote chemoautotrophy expressed a number of putative cell signaling and innate immunity genes, including pattern recognition receptors (PRRs), often associated with recognizing microbe-associated molecular patterns (MAMPs). Eighteen genes involved with innate immunity, cell signaling, cell stress and metabolite exchange were further analyzed using qPCR. PRRs, including five peptidoglycan recognition proteins and a Toll-like receptor, were expressed significantly higher in the trophosome compared to the plume. Although PRRs are often associated with mediating host responses to infection by pathogens, the differences in expression between the plume and trophosome also implicate similar mechanisms of microbial recognition in interactions between the host and symbiont. We posit that regulation of this association involves a molecular “dialogue” between the partners that includes interactions between the host’s innate immune system and the symbiont

Sources of variability in levels and exposure to trihalomethanes.

International audienceIn the framework of a cohort study of pregnant women conducted in Brittany (France), we assessed the exposure to trihalomethanes (THM) during pregnancy in a subset by evaluating (1) potential sources of variability in household THM levels; (2) the between- and within-subject variability in THM levels; (3) THM levels in swimming pools; and (4) the role of water-related habits on total THM uptake. We visited 109 women from the ongoing cohort study at home for an interview and collection of tap water from October to December 2004. Forty-three of them were re-contacted to obtain a second tap water sample in April-May 2005. We designed a questionnaire to collect individual information on source and amount of drinking water, frequency of showering, bathing, and swimming pool attendance, and household characteristics. We obtained 282 THM measurements, 152 specifically for the study and 130 from a regulatory agency. Personal information and environmental data were combined using two methodologies (method 1 using regulatory data and method 2 using our THM measurements) with a different set of assumptions. We calculated ingestion, showering, bathing, and swimming pool THM uptakes and added up those uptakes to calculate total THM uptake. Average THM levels from our measurements in October, November-December, and April-May were 61.3, 45.1, and 54.5 microg/l, respectively. Geographical variability was low and characteristics of the household did not influence THM levels. Within-subject variability in THM levels was three times higher than between-subject variability. Average THM level in swimming pools was 80.4 microg/l. Average water consumption during pregnancy was 1.9l/day. The source of the household drinking water was 90% bottled, 8% municipal, and 2% from other sources. Forty-seven per cent attended swimming pools during pregnancy. Using method 1, the geometric mean of total THM uptake was 0.93 microg/day. Showering contributed 64%, swimming in pools 23%, bathing 12%, and drinking water 1% to the total THM uptake. In a setting with low geographical variability and limited environmental measurements, individual data is highly relevant to determine personal THM exposure and uptake. In a population that mainly drinks bottled water (e.g., pregnant women), individual THM uptakes are dominated by inhalation and dermal absorption during, showering, swimming in pools, and bathing

Benefit of infliximab reintroduction after successive failure of infliximab and adalimumab in Crohn's disease.

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The outcome of infliximab dose doubling in 157 patients with ulcerative colitis after loss of response to infliximab.

International audienceOptimising infliximab therapy is recommended in inflammatory bowel disease (IBD) patients who lose response to infliximab; however, there are no data on the outcome of ulcerative colitis (UC) patients after doubling the dose. To determine the efficacy and safety of infliximab dose doubling in UC patients with a loss of response to infliximab. From January 2006 to May 2013, we retrospectively reviewed the outcome of the consecutive UC patients who were treated with infliximab dose doubling (10 mg/kg) for loss of response in four French academic centres. The clinical response and remission were assessed. A composite event-free survival analysis was performed using the log-rank test and the Cox model. One hundred and fifty-seven patients [84 males; median age 37. 6 (IQR 28.2-49.4) years] were included. The median follow-up after infliximab dose doubling was 1.8 (1.0-3.1) years. At weeks 8 and 24, 55% and 43% of the patients achieved a clinical response respectively. The probabilities of the event-free survival were 71%, 61% and 55% at 6 months, 1 year and 2 years respectively. In the multivariate analysis, the predictors of infliximab dose doubling failure were the absence of the introduction of an immunomodulator concomitantly to dose doubling, a partial Ulcerative Colitis Disease Activity Index >6, a C-reactive protein level >10 mg/L, a leucocyte count >8000/mm(3) and a haemoglobin level <12.5 g/dL. Adverse events were reported in 12 patients (8%). Infliximab dose doubling led to short- and long-term event-free survival in UC patients, who had a loss of response to infliximab, in greater than 50% of the cases. The benefits of such a strategy were significantly improved by adding a concomitant immunomodulator