Search

Tularemia, caused by the bacterium Francisella tularensis, where F. tularensis subspecies holarctica has long been the cause of endemic disease in parts of northern Sweden. Despite this, our understanding of the natural life-cycle of the organism is still limited. During three years, we collected surface water samples (n = 341) and sediment samples (n = 245) in two areas in Sweden with endemic tularemia. Real-time PCR screening demonstrated the presence of F. tularenis lpnA sequences in 108 (32%) and 48 (20%) of the samples, respectively. The 16S rRNA sequences from those samples all grouped to the species F. tularensis. Analysis of the FtM19InDel region of lpnA-positive samples from selected sampling points confirmed the presence of F. tularensis subspecies holarctica-specific sequences. These sequences were detected in water sampled during both outbreak and nonoutbreak years. Our results indicate that diverse F. tularensis-like organisms, including F. tularensis subsp. holarctica, persist in natural waters and sediments in the investigated areas with endemic tularemia.

INTRODUCTION: Collagen-induced arthritis (CIA) is a mouse model for rheumatoid arthritis (RA) and is induced after immunization with type II collagen (CII). CIA, like RA, is an autoimmune disease leading to destruction of cartilage and joints, and both the priming and inflammatory phases have been suggested to be dependent on proteases. In particular, the cysteine proteases have been proposed to be detrimental to the arthritic process and even immunomodulatory. A natural inhibitor of cysteine proteases is cystatin C. METHODS: Cystatin C-deficient, sufficient and heterozygous mice were tested for onset, incidence and severity of CIA. The effect of cystatin C-deficiency was further dissected by testing the inflammatory effector phase of CIA; that is, collagen antibody-induced arthritis model and priming phase, that is, T cell response both in vivo and in vitro. In addition, in order to determine the importance of T cells and antigen-presenting cells (APCs), these cell populations were separated and in vitro T cell responses determined in a mixed co-culture system. Finally, flow cytometry was used in order to further characterize cell populations in cystatin C-deficient mice. RESULTS: Here, we show that mice lacking cystatin C, develop arthritis at a higher incidence and an earlier onset than wild-type controls. Interestingly, when the inflammatory phase of CIA was examined independently from immune priming then cystatin C-deficiency did not enhance the arthritis profile. However, in line with the enhanced CIA, there was an increased T cell and B cell response as delayed-type hypersensitivity reaction and anti-CII antibody titers were elevated in the cystatin C-deficient mice after immunization. In addition, the ex vivo naive APCs from cystatin C-deficient mice had a greater capacity to stimulate T cells. Interestingly, dendritic cells had a more activated phenotype in naive cystatin C-deficient mice. CONCLUSIONS: The lack of cystatin C enhances CIA and primarily affec

Reduced capacity to produce ROS increases the severity of T cell-dependent arthritis in both mice and rats with polymorphisms in neutrophil cytosolic factor 1 (Ncf1) (p47phox). Since T cells cannot exert oxidative burst, we hypothesized that T cell responsiveness is downregulated by ROS produced by APCs. Macrophages have the highest burst capacity among APCs, so to study the effect of macrophage ROS on T cell activation, we developed transgenic mice expressing functional Ncf1 restricted to macrophages. Macrophage-restricted expression of functional Ncf1 restored arthritis resistance to the level of that of wild-type mice in a collagen-induced arthritis model but not in a T cell-independent anti-collagen antibody-induced arthritis model. T cell activation was downregulated and skewed toward Th2 in transgenic mice. In vitro, IL-2 production and T cell proliferation were suppressed by macrophage ROS, irrespective of T cell origin. IFN-gamma production, however, was independent of macrophage ROS but dependent on T cell origin. These effects were antigen dependent but not restricted to collagen type II. In conclusion, macrophage-derived ROS play a role in T cell selection, maturation, and differentiation, and also a suppressive role in T cell activation, and thereby mediate protection against autoimmune diseases like arthritis.

QC 20100525

The alkylketene dimer (AKD) wax dispersion is introduced in the wet-end of a paper machine, and during drying it spreads and anchors to the fiber surface. Direct observation of the surface diffusion of the AKD wax at paper surfaces was obtained using X-ray photoelectron spectroscopy imaging technique. An AKD diffusion of approximately 400 μm was observed at a paper surface that was stored for 3 h at 80 °C. This gives a diffusion coefficient of approximately 10−11 m2 s−1. Storage for 1 week at room temperature also showed a remarkable spreading of AKD.

MHC class II molecules are not normally expressed on the cell surface of placental cells. This absence of class II molecules is assumed to be of importance for mammalian reproduction, since such expression is likely to increase the risk of harmful anti-pl, Addresses: Arvola M, Uppsala Univ, Dept Anim Dev & Genet, Norbyvagen 18A, S-75236 Uppsala, Sweden. Uppsala Univ, Dept Anim Dev & Genet, S-75236 Uppsala, Sweden. Univ Lund, Dept Cell & Mol Biol, Sect Med Inflammat Res, Lund, Sweden.

Transcriptional silencing can reflect heritable, epigenetic inactivation of genes, either singly or in groups, during the life-time of an organism. This phenomenon is exemplified by parent-of-origin-specific inactivation events (genomic imprinting) for a subset of mammalian autosomal genes, such as H19. Very little is known, however, about the timing and mechanism(s) of silencing of the paternal H19 allele during mouse development. Using a novel in situ approach, we present evidence that the silencing of the paternal H19 allele is progressive in the trophectodermal lineage during early mouse development and generates variegated expression patterns. The silencing process apparently involves recruitment of histone deacetylases since the mosaic paternal-specific H19 expression reappears in trichostatin A-treated mouse conceptuses, undergoing in vitro organogenesis. Moreover, the paternal H19 alleles of PatDup.d7 placentas, in which a region encompassing the H19 locus of chromosome 7 is bipaternally derived, partially escape the silencing process and are expressed in a variegated manner. We suggest that allele-specific silencing of H19 share some common features with chromatin-mediated silencing in position-effect variegation.

Addresses: Mattsson R, Univ Lund, Dept Inflammat Res, Lund, Sweden. Univ Lund, Dept Inflammat Res, Lund, Sweden. Dept Anim Dev & Genet, Uppsala, Sweden.

Trophoblast cells do not normally express major histocompatibility complex (MHC) class II antigens during placental development in either mice or rats. We have previously observed that in vive treatment of pregnant mice with interferon-gamma (IFN gamma) i, Addresses: UPPSALA UNIV, DEPT ANIM DEV & GENET, S-75236 UPPSALA, SWEDEN. LUND UNIV, DEPT MED INFLAMMAT RES, S-22100 LUND, SWEDEN.

PROBLEM: Neonatal mice nursed by dams lacking immunoglobulins (Igs) may often suffer from lethal runting if raised under conventional conditions. The present study was per formed in order to clarify a) the cause of the wasting syndrome and b) the protecti, Addresses: Gustafsson E, UPPSALA UNIV, DEPT ANIM DEV & GENET, NORBYVAGEN 18A, S-75236 UPPSALA, SWEDEN. NATL VET INST, DEPT VIROL, S-75123 UPPSALA, SWEDEN. LUND UNIV, DEPT MED INFLAMMAT RES, LUND, SWEDEN.

Members of the nuclear hormone receptor gene family of transcription factors have been shown to be expressed in characteristic patterns during mouse organogenesis and postnatal development. Using an RT-PCR based screening assay, we have identified nuclear, Addresses: KAROLINSKA INST, DEPT MED NUTR, NOVUM F60, S-14186 HUDDINGE, SWEDEN. UPPSALA UNIV, DEPT ANIM DEV & GENET, S-75236 UPPSALA, SWEDEN. KAROBIO AB, S-14186 HUDDINGE, SWEDEN.

Immunization of mice with rat type II collagen (CII), a cartilage-specific protein, leads to development of collagen-induced arthritis (CIA), a model for rheumatoid arthritis. To define the interaction between the immune system and cartilage, we produced, Addresses: Malmstrom V, LUND UNIV, DEPT CELL & MOLEC BIOL, SECT MED INFLAMMAT RES, BOX 94, S-22100 LUND, SWEDEN. UNIV ERLANGEN NURNBERG, DEPT INTERNAL MED 3, W-8520 ERLANGEN, GERMANY. UNIV UPPSALA, DEPT ANIM DEV & GENET, UPPSALA, SWEDEN. TURKU UNIV, DEPT