An Experimental Model of Cutaneous Infection Induced by Superantigen-Producing Staphylococcus aureus

Skin infections caused by Staphylococcus aureus, such as erysipelas, are commonly occurring, painful, and costly for society. Despite the high prevalence of this condition, little is known about the host immune responsiveness and bacterial virulence factors during S. aureus dermatitis. We present here a mouse model of infectious dermatitis in which S. aureus is inoculated by an intracutaneous injection to the shaved back of NMRI mice. Visible skin inflammation, characterized by redness and swelling, was noted 48 h after inoculation of staphylococci in mice that received 2 × 108 colony-forming units of S. aureus. Microscopic evaluation revealed a dermal and subcutaneous infiltrate rich in macrophages and neutrophilic granulocytes already within 6 h after inoculation. A sparse influx of T lymphocytes was noted somewhat later. Bacterial cultures from skin revealed high numbers of staphylococci early after inoculation, with a successive decline during 2 wk follow-up. Total white blood cell count as well as the number of polymorphonuclear leukocytes peaked 2 d after bacterial inoculation. Also, serum interleukin-6 levels peaked within 2 d, with a 10-fold increase compared to non-infected control mice, indicating a systemic reaction to skin infection. The role of toxic shock syndrome toxin 1 in the pathogenesis of the dermatitis was assessed using isogenic S. aureus strains. Even though the gross inflammatory skin reaction was similar for mice infected with either of the strains, it was apparent that bacteria secreting toxic shock syndrome toxin 1 preferentially triggered influx of T lymphocytes to the skin. In addition, mice inoculated with staphylococci producing toxic shock syndrome toxin 1 showed a weight decrease during the experiment whereas mice inoculated with the isogenic strain showed a weight increase. This model of staphylococcal dermatitis will enable future in-depth studies regarding the host–bacterium relationship

Minority Economic Development: The Problem of Business Failures

Inflammatory pseudotumour is a rare condition that can affect various organs. The clinical and histologic appearance of the pseudotumour may mimic haematological, lymphoproliferative, paraneoplastic or malignant processes. A previously healthy 39-year-old man presented with nephrotic syndrome. He had a history of headaches, nausea and swollen ankles. Computed tomography of the abdomen revealed a 6-cm mass in the spleen. Following a renal biopsy, a diagnosis of membranoproliferative glomerulonephritis (MPGN) type I was made. Splenectomy was performed and the examination revealed a mixed population of lymphocytes with predominantly T-cells, B-cells and lymphoplasmacytoid cells. Immunostaining confirmed that the small cells were mostly T-cells positive for all T-cell markers including CD2, CD3, CD4, CD5, CD7 and CD8. A diagnosis of inflammatory pseudotumour was established. The removal of the spleen was followed by remission of glomerulonephritis, but it was complicated by a subphrenic abscess and pneumonia. This association between an inflammatory pseudotumour of the spleen and MPGN has not been previously described. Abnormal immune response due to the inflammation leading to secondary glomerulonephritis might be the main pathogenic mechanism

Staphylococcus aureus synthesizes adenosine to escape host immune responses

Staphylococcus aureus infects hospitalized or healthy individuals and represents the most frequent cause of bacteremia, treatment of which is complicated by the emergence of methicillin-resistant S. aureus. We examined the ability of S. aureus to escape phagocytic clearance in blood and identified adenosine synthase A (AdsA), a cell wall–anchored enzyme that converts adenosine monophosphate to adenosine, as a critical virulence factor. Staphylococcal synthesis of adenosine in blood, escape from phagocytic clearance, and subsequent formation of organ abscesses were all dependent on adsA and could be rescued by an exogenous supply of adenosine. An AdsA homologue was identified in the anthrax pathogen, and adenosine synthesis also enabled escape of Bacillus anthracis from phagocytic clearance. Collectively, these results suggest that staphylococci and other bacterial pathogens exploit the immunomodulatory attributes of adenosine to escape host immune responses

Role of Glomerular Proteoglycans in IgA Nephropathy

Mesangial matrix expansion is a prominent feature of the most common form of glomerulonephritis, IgA nephropathy (IgAN). To find molecular markers and improve the understanding of the disease, the gene and protein expression of proteoglycans were investigated in biopsies from IgAN patients and correlated to clinical and morphological data. We collected and microdissected renal biopsies from IgAN patients (n = 19) and from healthy kidney donors (n = 14). Patients were followed for an average time of 4 years and blood pressure was according to target guidelines. Distinct patterns of gene expression were seen in glomerular and tubulo-interstitial cells. Three of the proteoglycans investigated were found to be of special interest and upregulated in glomeruli: perlecan, decorin and biglycan. Perlecan gene expression negatively correlated to albumin excretion and progress of the disease. Abundant decorin protein expression was found in sclerotic glomeruli, but not in unaffected glomeruli from IgAN patients or in controls. Transforming growth factor beta (TGF-β), known to interact with perlecan, decorin and biglycan, were upregulated both on gene and protein level in the glomeruli. This study provides further insight into the molecular mechanisms involved in mesangial matrix expansion in IgAN. We conclude that perlecan is a possible prognostic marker for patients with IgAN. In addition, the up-regulation of biglycan and decorin, as well as TGF-β itself, indicate that regulation of TGF-β, and other profibrotic markers plays a role in IgAN pathology

Depletion of Dendritic Cells Enhances Innate Anti-Bacterial Host Defense through Modulation of Phagocyte Homeostasis

Dendritic cells (DCs) as professional antigen-presenting cells play an important role in the initiation and modulation of the adaptive immune response. However, their role in the innate immune response against bacterial infections is not completely defined. Here we have analyzed the role of DCs and their impact on the innate anti-bacterial host defense in an experimental infection model of Yersinia enterocolitica (Ye). We used CD11c-diphtheria toxin (DT) mice to deplete DCs prior to severe infection with Ye. DC depletion significantly increased animal survival after Ye infection. The bacterial load in the spleen of DC-depleted mice was significantly lower than that of control mice throughout the infection. DC depletion was accompanied by an increase in the serum levels of CXCL1, G-CSF, IL-1α, and CCL2 and an increase in the numbers of splenic phagocytes. Functionally, splenocytes from DC-depleted mice exhibited an increased bacterial killing capacity compared to splenocytes from control mice. Cellular studies further showed that this was due to an increased production of reactive oxygen species (ROS) by neutrophils. Adoptive transfer of neutrophils from DC-depleted mice into control mice prior to Ye infection reduced the bacterial load to the level of Ye-infected DC-depleted mice, suggesting that the increased number of phagocytes with additional ROS production account for the decreased bacterial load. Furthermore, after incubation with serum from DC-depleted mice splenocytes from control mice increased their bacterial killing capacity, most likely due to enhanced ROS production by neutrophils, indicating that serum factors from DC-depleted mice account for this effect. In summary, we could show that DC depletion triggers phagocyte accumulation in the spleen and enhances their anti-bacterial killing capacity upon bacterial infection

Gut Microbiota and Inflammation

Systemic and local inflammation in relation to the resident microbiota of the human gastro-intestinal (GI) tract and administration of probiotics are the main themes of the present review. The dominating taxa of the human GI tract and their potential for aggravating or suppressing inflammation are described. The review focuses on human trials with probiotics and does not include in vitro studies and animal experimental models. The applications of probiotics considered are systemic immune-modulation, the metabolic syndrome, liver injury, inflammatory bowel disease, colorectal cancer and radiation-induced enteritis. When the major genomic differences between different types of probiotics are taken into account, it is to be expected that the human body can respond differently to the different species and strains of probiotics. This fact is often neglected in discussions of the outcome of clinical trials with probiotics

Att sälja en journalist – Hur dagstidningar marknadsför sina journalister

Att sälja en journalist – Hur dagstidningar marknadsför sina journalister Written by: Jonatan Fjelstad & Viktor Mölne Bachelor´s degree of Journalism Department of Journalism, Media & Communication. Autumn term 2013 University of Gothenburg The purpose of this study is to determine if Swedish newspapers has increased the visibility of their own journalists between the years 2000 and 2012 and if that’s the case how they have done so. By doing so we hope to shed some light on how individual journalists are increasingly personalized and how this can be part of the newspapers branding strategy. The journalist’s personal brands have been the subject of more research lately. But from the perspective of the newspaper itself, not much has been studied. We have utilized a broad theoretical approach with its foundation in commercialization and some personalization and visualization. We also lean quite heavily on research focused on branding, especially branding for media corporations. The nature of the study is quantitative and we have studied three Swedish newspapers Svenska Dagbladet, Aftonbladet and Expressen. We have coded all the respective newspapers opinion material and plugs, everything that mentions the material in the paper or other media forms, for individual journalists. In total 1041 units of analysis data has been collected and analysed. Our results show that there is an increase in the amount of mentioning of individual journalists in plugs, both stand-alone and in context of other articles. In 2012 we saw almost 5 times as many as in 2000. The big majority of these were to columns and other opinionated material. To our surprise, however, we found have found no signs that opinionated material is used to promote the work of the newspapers own journalists in any greater extent

Host-bacterium relationship in staphylococcal skin infection

Skin infections caused by Staphylococcus aureus are commonly occuring, both in the community and in hospitals. Despite the high prevalence of this condition, little is known about the host immune responsiveness and bacterial virulence factors during S. aureus skin infection. To enable an in-depth understanding of the host-bacterium relationship, we assessed a murine model of cutaneous infection. Mice inoculated intradermally with high numbers of staphylococci (108 CFU) displayed clinical and histopathological signs of local inflammation, but lacked signs of sepsis. In this model, the role of a superantigen, TSST-1, was assessed using isogenic S. aureus strains. Mice inoculated with the TSST-1-producing strain showed a weight decrease and a preferential influx of CD4+T lymphocytes to the skin.To assess the role of neutrophils in staphylococcal skin infection, mice were given granulocyte-depleting monoclonal antibody prior to intracutaneous inoculation with staphylococci, resulting in substantial early neutropenia. The granulocyte-depleted mice displayed a more severe clinical infection, a higher bacterial burden in the blood and in the skin, generalized signs of inflammation and a weight loss. Early recruitment of neutrophils and possibly phagocytosis in the initial stages of S. aureus infection was concluded to be critical for the outcome of staphylococcal skin infection.The high number of gamma/delta-expressing T cells found in the epithelial lining layer suggests that they form a first line of defense against invading pathogens. To evaluate the role of gamma/delta T cell receptor(TCR)-expressing lymphocytes in cutaneous infection caused by S. aureus, mice lacking gamma/delta TCR-expressing cells were inoculated intradermally with S. aureus and compared with S. aureus-infected congenic control mice. We observed early and transient deficiency in the bacterial elimination in gamma/delta T cell deficient mice, which supports the notion that cutaneous gamma/delta T cells act as an early barrier to prevent staphylococcal infections of the skin.Bacterial DNA and synthetic oligodeoxynucleotides (ODNs) containing CpG sequences, mimicking prokaryotic DNA, have recently been shown to exert potent immunostimulatory properties. Bacterial DNA from S. aureus and CpG-containing ODNs were injected intradermally, giving rise to an inflammatory infiltrate. Depletion of monocytes/macrophages resulted in a significant decrease in the severity of inflammation, which suggests that macrophages play a central role in inflammatory responses in the skin following exposure to bacterial DNA. In summary, our results suggest that bacterial DNA is an important virulence determinant and inflammatory stimulus during skin infections.In this model of cutaneous staphylococcal infection, we have assessed the role of some bacterial virulence factors, such as bacterial DNA and TSST-1, and the importance of some host immune cells, such as neutrophils and gamma/delta T cells, showing crucial host-bacterium relationship in the development of inflammatory skin lesions