Colonic macrophages are considered to be major effectors of inflammatory bowel diseases (IBDs) and the control of gut inflammation through C-type lectin receptors is an emerging concept. We show that ...during colitis, the loss of dectin-1 on myeloid cells prevents intestinal inflammation, while the lack of mannose receptor (MR) exacerbates it. A marked increase in dectin-1 expression in dextran sulfate sodium (DSS)-exposed MR-deficient mice supports the critical contribution of dectin-1 to colitis outcome. Dectin-1 is crucial for Ly6ChighCCR2high monocyte population enrichment in the blood and their recruitment to inflamed colon as precursors of inflammatory macrophages. Dectin-1 also promotes inflammasome-dependent interleukin-1β (IL-1β) secretion through leukotriene B4 production. Interestingly, colonic inflammation is associated with a concomitant overexpression of dectin-1/CCL2/LTA4H and downregulation of MR on macrophages from IBD patients. Thus, MR and dectin-1 on macrophages are important mucosal inflammatory regulators that contribute to the intestinal inflammation.
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•Colitis is attenuated in mice with dectin-1−/− macrophages and severe in mice with MR−/− macrophages•Dectin-1 on macrophages mediates recruitment of inflammatory classical monocytes in the gut•Dectin-1 positively controls inflammatory phenotype of intestinal macrophages during colitis•Gut inflammation in IBD patients is linked to dectin-1 induction and reduced MR
Rahabi et al. show a critical contribution of dectin-1 on macrophages in intestinal inflammation. Dectin-1 is involved in Ly6ChighCCR2high monocyte population enrichment in the blood and their recruitment to inflamed colon, macrophage differentiation toward inflammatory phenotype, and inflammasome-dependent IL-1β secretion through LTB4.
Aim: Invasive species are of increasing global concern. Nevertheless, the mechanisms driving further distribution after the initial establishment of non-native species remain largely unresolved, ...especially in marine systems. Ocean currents can be a major driver governing range occupancy, but this has not been accounted for in most invasion ecology studies so far. We investigate how well initial establishment areas are interconnected to later occupancy regions to test for the potential role of ocean currents driving secondary spread dynamics in order to infer invasion corridors and the source–sink dynamics of a non-native holoplanktonic biological probe species on a continental scale. Location: Western Eurasia. Time period: 1980s–2016. Major taxa studied: 'Comb jelly' Mnemiopsis leidyi. Methods: Based on 12,400 geo-referenced occurrence data, we reconstruct the invasion history of M. leidyi in western Eurasia. We model ocean currents and calculate their stability to match the temporal and spatial spread dynamics with large-scale connectivity patterns via ocean currents. Additionally, genetic markers are used to test the predicted connectivity between subpopulations. Results: Ocean currents can explain secondary spread dynamics, matching observed range expansions and the timing of first occurrence of our holoplanktonic non-native biological probe species, leading to invasion corridors in western Eurasia. In northern Europe, regional extinctions after cold winters were followed by rapid recolonizations at a speed of up to 2,000 km per season. Source areas hosting year-round populations in highly interconnected regions can re-seed genotypes over large distances after local extinctions. Main conclusions: Although the release of ballast water from container ships may contribute to the dispersal of non-native species, our results highlight the importance of ocean currents driving secondary spread dynamics. Highly interconnected areas hosting invasive species are crucial for secondary spread dynamics on a continental scale. Invasion risk assessments should consider large-scale connectivity patterns and the potential source regions of non-native marine species.
Background and Purpose
Thrombin is massively released upon tissue damage associated with bleeding or chronic inflammation. The effects of this thrombin on tissue regrowth and repair has been scarcely ...addressed and only in cancer cell lines. Hence, the purpose of the present study was to determine thrombin's pharmacological effects on human intestinal epithelium growth, proliferation and apoptosis, using three‐dimensional cultures of human colon organoids.
Experimental Approach
Crypts were isolated from human colonic resections and cultured for 6 days, forming human colon organoids. Cultured organoids were exposed to 10 and 50 mU·mL−1 of thrombin, in the presence or not of protease‐activated receptor (PAR) antagonists. Organoid morphology, metabolism, proliferation and apoptosis were followed.
Key Results
Thrombin favoured organoid maturation leading to a decreased number of immature cystic structures and a concomitant increased number of larger structures releasing cell debris and apoptotic cells. The size of budding structures, metabolic activity and proliferation were significantly reduced in organoid cultures exposed to thrombin, while apoptosis was dramatically increased. Both PAR1 and PAR4 antagonists inhibited apoptosis regardless of thrombin doses. Thrombin‐induced inhibition of proliferation and metabolic activity were reversed by PAR4 antagonist for thrombin's lowest dose and by PAR1 antagonist for thrombin's highest dose.
Conclusions and Implications
Overall, our data suggest that the presence of thrombin in the vicinity of human colon epithelial cells favours their maturation at the expense of their regenerative capacities. Our data point to thrombin and its two receptors PAR1 and PAR4 as potential molecular targets for epithelial repair therapies.
Imbalance between proteases and their inhibitors plays a crucial role in the development of Inflammatory Bowel Diseases (IBD). Increased elastolytic activity is observed in the colon of patients ...suffering from IBD. Here, we aimed at identifying the players involved in elastolytic hyperactivity associated with IBD and their contribution to the disease. We revealed that epithelial cells are a major source of elastolytic activity in healthy human colonic tissues and this activity is greatly increased in IBD patients, both in diseased and distant sites of inflammation. This study identified a previously unrevealed production of elastase 2A (ELA2A) by colonic epithelial cells, which was enhanced in IBD patients. We demonstrated that ELA2A hyperactivity is sufficient to lead to a leaky epithelial barrier. Epithelial ELA2A hyperactivity also modified the cytokine gene expression profile with an increase of pro-inflammatory cytokine transcripts, while reducing the expression of pro-resolving and repair factor genes. ELA2A thus appears as a novel actor produced by intestinal epithelial cells, which can drive inflammation and loss of barrier function, two essentials pathophysiological hallmarks of IBD. Targeting ELA2A hyperactivity should thus be considered as a potential target for IBD treatment.
Hepatitis C virus (HCV) infection is associated with lymphoproliferative disorders and B-cell non-Hodgkin lymphomas (B-NHLs). Evaluation of the efficacy and safety profiles of different antiviral ...therapies in HCV patients with B-NHL is warranted.
First, we evaluated the sustained virologic response (SVR) and safety of Peg-interferon-alpha (Peg-IFN) + ribavirin +/- first protease inhibitors (PI1s) therapy in 61 HCV patients with B-NHL enrolled in a nationwide observational survey compared with 94 matched HCV-infected controls without B-NHL. In a second series, interferon-free regimens using a newly optimal combination therapy with direct-acting antiviral drugs (DAAs) were evaluated in 10 patients with HCV and B-NHL.
The main lymphoma type was diffuse large B-cell lymphoma (38%) followed by marginal zone lymphoma (31%). In the multivariate analysis, patients with B-NHL treated by Peg-IFN-based therapy exhibited a greater SVR rate compared with controls, 50.8% vs 30.8%, respectively, p<0.01, odds ratio (OR) = 11.2 2.3, 52.8. B-NHL response was better (p = 0.02) in patients with SVR (69%) than in patients without SVR (31%). Premature discontinuation of Peg-IFN-based therapy was significantly more frequent in the B-NHL group (19.6%) compared with the control group (6.3%), p<0.02. Overall, survival was significantly enhanced in the controls than in the B-NHL group (hazard ratio = 34.4 3.9, 304.2, p< 0.01). Using DAAs, SVR was achieved in 9/10 patients (90%). DAAs were both well tolerated and markedly efficient.
The virologic response of HCV-associated B-NHL is high. Our study provides a comprehensive evaluation of different strategies for the antiviral treatment of B-NHL associated with HCV infection.
species have been associated with recurrent mass mortalities of juvenile oysters
threatening oyster farming worldwide. However, knowledge of the ecology of pathogens in affected oyster farming areas ...remains scarce. Specifically, there are no data regarding (i) the environmental reservoirs of
populations pathogenic to oysters, (ii) the environmental factors favoring their transmission, and (iii) the influence of oyster farming on the persistence of those pathogens. This knowledge gap limits our capacity to predict and mitigate disease occurrence. To address these issues, we monitored
species potentially pathogenic to
in 2013 and 2014 in the Thau Lagoon, a major oyster farming region in the coastal French Mediterranean. Sampling stations were chosen inside and outside oyster farms. Abundance and composition of phyto-, microzoo-, and mesozooplankton communities were measured monthly. The spatial and temporal dynamics of plankton and
species were compared, and positive correlations between plankton species and vibrios were verified by qPCR on isolated specimens of plankton.
was present in the water column over both years, whereas
was mostly found in 2013 and
was never detected. Moreover,
and
were found both as free-living or plankton-attached vibrios 1 month after spring mortalities of the oyster juveniles. Overall,
was associated with temperature and plankton composition, whereas
correlated with plankton composition only. The abundance of
species in the water column was similar inside and outside oyster farms, suggesting important spatial dispersion of pathogens in surrounding areas. Remarkably, a major increase in
and
was measured in the sediment of oyster farms during cold months. Thus, a winter reservoir of pathogenic vibrios could contribute to their ecology in this Mediterranean shellfish farming ecosystem.
This study aims at quantifying and characterising microplastics (MP) distribution in the water column of the NW Mediterranean Sea as well as MP ingestion by the 2 main planktivorous fish of the area, ...sardine and anchovy.
Debris of similar sizes were found in all water column samples and in all but 2 fish guts (out of 169). MP were found in 93% of water column samples with an average concentration of 0.23 ± 0.20 MP·m−3, but in only 12% of sardines (0.20 ± 0.69 MP·ind−1) and 11% of anchovies (0.11 ± 0.31 MP·ind−1). Fibres were the only shape of MP encountered and polyethylene terephthalate was the main polymer identified in water columns (61%), sardines (71%) and anchovies (89%).
This study confirms the ubiquity of MP in the Mediterranean Sea and imparts low occurrence in fish digestive tracts.
•Microplastics were studied in the NW Mediterranean Sea using 17 stations in 2015.•Microplastic concentration averaged 0.23 ± 0.20 MP·m−3 in the water column.•Microplastic ingestion occurred in only 11–12% of anchovies and sardines.•The main polymer type recovered in each sample was polyethylene terephtalate.•Fibres were the only microplastic shape encountered.
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