Host and microbiota interactions are critical for development of murine Crohn's-like ileitis.

Deregulation of host-microbiota interactions in the gut is a pivotal characteristic of Crohn's disease. It remains unclear, however, whether commensals and/or the dysbiotic microbiota associated with pathology in humans are causally involved in Crohn's pathogenesis. Here, we show that Crohn's-like ileitis in Tnf(ΔARE/+) mice is microbiota-dependent. Germ-free Tnf(ΔARE/+) mice are disease-free and the microbiota and its innate recognition through Myd88 are indispensable for tumor necrosis factor (TNF) overexpression and disease initiation in this model. The epithelium of diseased mice shows no major defects in mucus barrier and paracellular permeability. However, Tnf(ΔARE/+) ileitis associates with the reduction of lysozyme-expressing Paneth cells, mediated by adaptive immune effectors. Furthermore, we show that established but not early ileitis in Tnf(ΔARE/+) mice involves defective expression of antimicrobials and dysbiosis, characterized by Firmicutes expansion, including epithelial-attaching segmented filamentous bacteria, and decreased abundance of Bacteroidetes. Microbiota modulation by antibiotic treatment at an early disease stage rescues ileitis. Our results suggest that the indigenous microbiota is sufficient to drive TNF overexpression and Crohn's ileitis in the genetically susceptible Tnf(ΔARE/+) hosts, whereas dysbiosis in this model results from disease-associated alterations including loss of lysozyme-expressing Paneth cells.

MUGEN mouse database; animal models of human immunological diseases.

The MUGEN mouse database (MMdb) (www.mugen-noe.org/database/) is a database of murine models of immune processes and immunological diseases. Its aim is to share and publicize information on mouse strain characteristics and availability from participating institutions. MMdb's basic classification of models is based on three major research application categories: Models of Human Disease, Models of Immune Processes and Transgenic Tools. Data on mutant strains includes detailed information on affected gene(s), mutant allele(s) and genetic background (DNA origin, gene targeted, host and backcross strain background). Each gene/transgene index also includes IDs and direct links to Ensembl, ArrayExpress, EURExpress and NCBI's Entrez Gene database. Phenotypic description is standardized and hierarchically structured, based on MGI's mammalian phenotypic ontology terms. Availability (e.g. live mice, cryopreserved embryos, sperm and ES cells) is clearly indicated, along with handling and genotyping details (in the form of documents or hyperlinks) and all relevant contact information (including EMMA and Jax/IMSR hyperlinks where available). MMdb's design offers a user-friendly query interface and provides instant access to the list of mutant strains and genes. Database access is free of charge and there are no registration requirements for data querying.

Actin cytoskeleton dynamics linked to synovial fibroblast activation as a novel pathogenic principle in TNF-driven arthritis.

Rheumatoid arthritis is a chronic inflammatory disorder whose origin of defect has been the subject of extensive research during the past few decades. While a number of immune and non-immune cell types participate in the development of chronic destructive inflammation in the arthritic joint, synovial fibroblasts have emerged as key effector cells capable of modulating both joint destruction and propagation of inflammation. Ample evidence of aberrant changes in the morphology and biochemical behaviour of rheumatoid arthritis synovial fibroblasts have established the tissue evading and "transformed" character of this cell type. We have recently demonstrated that actin cytoskeletal rearrangements determine the pathogenic activation of synovial fibroblasts in modelled TNF-mediated arthritis, a finding correlating with similar gene expression changes which we observed in human rheumatoid arthritis synovial fibroblasts. Here, we show that pharmacological inhibition of actin cytoskeleton dynamics alters potential pathogenic properties of the arthritogenic synovial fibroblast, such as proliferation, migration and resistance to apoptosis, indicating novel opportunities for therapeutic intervention in arthritis. Recent advances in this field of research are reviewed and discussed.

Antiviral properties of isoborneol, a potent inhibitor of herpes simplex virus type 1.

Isoborneol, a monoterpene and a component of several plant essential oils, showed dual viricidal activity against herpes simplex virus 1 (HSV-1). First, it inactivated HSV-1 by almost 4 log10 values within 30 min of exposure, and second, isoborneol at a concentration of 0.06% completely inhibited viral replication, without affecting viral adsorption. Isoborneol did not exhibit significant cytotoxicity at concentrations ranging between 0.016% and 0.08% when tested against human and monkey cell lines. Isoborneol specifically inhibited glycosylation of viral polypeptides based on the following data: (1) the mature fully glycosylated forms of two viral glycoproteins gB and gD were not detected when the virus was replicated in the presence of isoborneol, (2) no major changes were observed in the glycosylation pattern of cellular polypeptides between untreated and isoborneol treated Vero cells, (3) isoborneol did not affect the glycosylation of gB produced from a copy of the gB gene resident in the cellular genome, and (4) other monoterpenes such as 1,8-cineole and borneol, a stereoisomer of isoborneol, did not inhibit HSV-1 glycosylation.