Nod2 protects the gut from spreading experimental colitis to small intestine

International audienceAbstract Background and Aims: Nucleotide Oligomerization Domain 2 (NOD2) mutations are key risk factors for Crohn’s disease (CD). NOD2 contributes to intestinal homeostasis by regulating innate and adaptive immunity together with intestinal epithelial function. However, the exact roles of NOD2 in CD and other NOD2-associated disorders remain poorly known. Methods: We initially observed that NOD2 expression was increased in epithelial cells away from inflamed areas in CD patients. To explore this finding, Nod2 mRNA expression, inflammation and cytokines expression were examined in the small bowel of wild-type (WT), Nod2 knockout and Nod2 mutant mice after rectal instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Results: In WT mice, Nod2 upregulation upstream to rectal injury was associated with pro-inflammatory cytokine expression but no overt histological inflammatory lesions. At the opposite, in Nod2 deficient mice, the inflammation spread from colitis to ileum and duodenum. Conclusions: Nod2 protects the gut from spreading colitis to small intestine

Nod2 protects remote small intestinal sites in case of colonic inflammation.

NOD2 mutations are key risk factors for Crohn’s disease (CD). NOD2 contributes to intestinal homeostasis by regulating innate and adaptive immunity together with intestinal epithelial function. However, the roles of NOD2 during gut inflammation is not known. We initially observed that NOD2 expression was increased in epithelial cells remote from inflamed areas in CD patients. To explore this finding, Nod2 mRNA expression, inflammation and gut permeability were examined in the small bowel of wild-type (WT), Nod2 knockout and Nod2 mutant mice after rectal instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS). In WT mice, Nod2 upregulation remote to rectal injury was associated with proinflammatory cytokine expression, recirculating CD4+ 46 T-cells, increased paracellular permeability and myosin like chain kinase activity. Nod2 knockout or mutation led to duodenitis and ileitis demonstrating the remote protective role of Nod2. Bone morrow stem cell (BMSC) transplantations indicated that the small intestinal inflammation was due to NOD2 loss in both hematopoietic and non-hematopoietic compartments. As a whole, WT but not mutant NOD2 prevents disease extension at sites remote from the initial intestinal injury

WEB 2.0 : 15 ans déjà et après ? : 7 pistes pour réenchanter Internet !

International audienceEn 15 ans, le Web 2.0 a radicalement transformé notre façon de travailler, de consommer, de vendre, de communiquer… Les technologies (mobile et tablette, 3G ou 4G, médias sociaux, big data, IA, etc.) ont bouleversé nos sphères de vie et notre rapport aux individus, à l’information, aux objets… 57 pionniers vous proposent d’explorer rétrospectivement les conséquences du digital sur notre société (économie, politique, juridique, culturel…). Le but : imaginer 7 pistes de réenchantement pour un futur numérique plus sain et plus responsable face à la domination des géants d’Internet, GAFA et BATX.La voix de 57 pionniers : Farid Arab . Thierry de Baillon . Christine Balagué . Éric Barbry . Beer Bergman . Olivier Berlingué . Nicolas Bermond . Fanny Berrebi . Michelle Blanc . Jérôme Bondu . Fadhila Brahimi . Frédéric Canevet . Dominique Cardon . Nicolas Celic . Cyrille Chaudoit . Jean-Pierre Corniou . Céline Crespin . André Dan . Yannis Delmas-Rigoutsos . Damien Douani . Antoine Dubuquoy . Jean-Philippe Encausse . Fabrice Epelboin . Olivier Ezratty . Isabelle Falque-Pierrotin . David Fayon . Mathieu Flaig . Cyrille Frank . Yann Gourvennec . David Guillocheau . Claudie Haigneré (Préface) . Olivier Iteanu . Henri Kaufman (Postface) . François Laurent . Yann Leroux . Éric Maillard . Vérone Mankou . Émilie Marquois . Grégory Maubon . Pierre Mawas . Pierre Métivier . Jean-Claude Morand . Ahmed Mehdi Omarouayache . Anthony Poncier . Grégory Pouy . PPC . Benoît Raphaël . Cyril Rimbaud . Vincent Rostaing . Jean-François Ruiz . Éric Seulliet . Serge Soudoplatoff . Virginie Spies . Yaëlle Teicher Stein . Pierre Tran . Pierre Vallet . Henri Verdier

A highly virulent variant of HIV-1 circulating in the Netherlands

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence