Infectious diseases and autoimmunity

Introduction: Autoimmunity occurs when the immune system recognizes and attacks host tissue. In addition to genetic factors, environmental triggers (in particular viruses, bacteria and other infectious pathogens) are thought to play a major role in the development of autoimmune diseases. Methodology: We searched PubMed, Cochrane, and Scopus without time limits for relevant articles. Results: In this review, we (i) describe the ways in which an infectious agent can initiate or exacerbate autoimmunity; (ii) discuss the evidence linking certain infectious agents to autoimmune diseases in humans; and (iii) describe the animal models used to study the link between infection and autoimmunity. Conclusions: Besides genetic predisposition to autoimmunity, viral and bacterial infections are known to be involved in the initiation and promotion of autoimmune diseases. These studies suggest that pathogens can trigger autoimmunity through molecular mimicry and their adjuvant effects during initiation of disease, and can promote autoimmune responses through bystander activation or epitope spreading via inflammation and/or superantigens.</br

Monoclonal antibodies against human CD34 antigens do not cross-react with ovine umbilical cord blood cells

CD34 is a cell surface glycoprotein expressed by hematopoietic progenitors and endothelial cells. It is widely used in the clinic for isolation of human hematopoietic stem cells. In recent years large animals are gaining increasing importance in biomedical research for the study and therapy of human diseases. Sheep has proved to be an useful experimental model for preclinical trials in transplantation procedures. Unfortunately, the lack of specie-specific monoclonal antibodies (MABS) recognizing hemopoietic progenitor cells hampers the use of this animal in experimental hematology. The aim of this paper was to determine whether commercial monoclonal antibodies specific for human CD34 molecule could cross-react with hematopoietic progenitor cells (HPC) present in sheep umbilical cord blood (UCB). Six anti-human CD34 MABS, recognizing the three different epitope classes, were tested in flow cytometry on purified mononuclear cells (MNC) isolated from cord blood of both species. None of the MABS used in this trial seemed to be able to identify HPC from sheep UCB. These data suggest that the panel of monoclonal antibodies used for cross reactivity detection has to be expanded with recently produced reagents. Further studies should be directed towards the production of ovine specific anti CD34 MABS

Functionalized multiwalled carbon nanotubes as ultrasound contrast agents

Ultrasonography is a fundamental diagnostic imaging tool in everyday clinical practice. Here, we are unique in describing the use of functionalized multiwalled carbon nanotubes (MWCNTs) as hyperechogenic material, suggesting their potential application as ultrasound contrast agents. Initially, we carried out a thorough investigation to assess the echogenic property of the nanotubes in vitro. We demonstrated their long-lasting ultrasound contrast properties. We also showed that ultrasound signal of functionalized MWCNTs is higher than graphene oxide, pristine MWCNTs, and functionalized single-walled CNTs. Qualitatively, the ultrasound signal of CNTs was equal to that of sulfur hexafluoride (SonoVue), a commercially available contrast agent. Then, we found that MWCNTs were highly echogenic in liver and heart through ex vivo experiments using pig as an animal model. In contrast to the majority of ultrasound contrast agents, we observed in a phantom bladder that the tubes can be visualized within a wide variety of frequencies (i.e., 5.5–10 MHz) and 12.5 MHz using tissue harmonic imaging modality. Finally, we demonstrated in vivo in the pig bladder that MWCNTs can be observed at low frequencies, which are appropriate for abdominal organs. Importantly, we did not report any toxicity of CNTs after 7 d from the injection by animal autopsy, organ histology and immunostaining, blood count, and chemical profile. Our results reveal the enormous potential of CNTs as ultrasound contrast agents, giving support for their future applications as theranostic nanoparticles, combining diagnostic and therapeutic modalities

Altered Immunoregulation in Rheumatoid Arthritis: The Role of Regulatory T Cells and Proinflammatory Th17 Cells and Therapeutic Implications

In recent years several studies investigated the role of T lymphocyte subpopulations in the pathogenesis of rheumatoid arthritis (RA). Pathogenic Th17 cells mediate pannus growth, osteoclastogenesis, and synovial neoangiogenesis; hence they are key players in the development of the disease. On the other hand, regulatory T (Treg) cells are a T cell subset whose peculiar function is to suppress autoreactive lymphocytes. The imbalance between Th17 and Treg cells has been identified as a crucial event in the pathogenesis of RA. In addition, the effects of currently employed RA therapeutic strategies on these lymphocyte subpopulations have been extensively investigated. This review article aims to discuss current knowledge on Treg and Th17 cells in RA and possible implications of their therapeutic targeting in this disorder

Methane emission and milk production of dairy cows grazing pastures rich in legumes or rich in grasses in Uruguay

Understanding the impact of changing pasture composition on reducing emissions of GHGs in dairy grazing systems is an important issue to mitigate climate change. The aim of this study was to estimate daily CH4 emissions of dairy cows grazing two mixed pastures with contrasting composition of grasses and legumes: L pasture with 60% legumes on Dry Matter (DM) basis and G pasture with 75% grasses on DM basis. Milk production and CH4 emissions were compared over two periods of two weeks during spring using eight lactating Holstein cows in a 2 × 2 Latin square design. Herbage organic matter intake (HOMI) was estimated by chromic oxide dilution and herbage organic matter digestibility (OMD) was estimated by faecal index. Methane emission was estimated by using the sulfur hexafluoride (SF6) tracer technique adapted to collect breath samples over 5-day periods. OMD (0.71) and HOMI (15.7 kg OM) were not affected by pasture composition. Milk production (20.3 kg/d), milk fat yield (742 g/d) and milk protein yield (667 g/d) were similar for both pastures. This may be explained by the high herbage allowance (30 kg DM above 5 cm/cow) which allowed the cows to graze selectively, in particular in grass sward. Similarly, methane emission expressed as absolute value (368 g/d or 516 L/d) or expressed as methane yield (6.6% of Gross Energy Intake (GEI)) was not affected by treatments. In conclusion, at high herbage allowance, the quality of the diet selected by grazing cows did not differ between pastures rich in legumes or rich in grasses, and therefore there was no effect on milk or methane production.Fil: Dini, Yoana. Universidad de la Republica; UruguayFil: Gere, José Ignacio. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Instituto de Física Arroyo Seco; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil; ArgentinaFil: Briano, Carolina. Universidad de la República; UruguayFil: Manetti, Martin Diego. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Córdoba; ArgentinaFil: Juliarena, María Paula. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Instituto de Física Arroyo Seco; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil; ArgentinaFil: Picasso, Valentin. Universidad de la República; UruguayFil: Gratton, Roberto. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Exactas. Instituto de Física Arroyo Seco; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil; ArgentinaFil: Astigarraga, Laura. Universidad de la República; Urugua

Low pH Activates the Vacuolating Toxin of Helicobacter pylori, Which Becomes Acid and Pepsin Resistant

The protein toxin VacA, produced by cytotoxic strains of Helicobacter pylori, causes a vacuolar degeneration of cells, which eventually die. VacA is strongly activated by a short exposure to acidic solutions in the pH 1.5-5.5 range, followed by neutralization. Activated VacA has different CD and fluorescence spectra and a limited proteolysis fragmentation pattern from VacA kept at neutral pH. Moreover, activated VacA is resistant to pH 1.5 and to pepsin. The relevance of these findings to pathogenesis of H. pylori-induced gastrointestinal ulcers is discussed

Absence of protein A expression is associated with higher capsule production in staphylococcal isolates

Staphylococcus aureus is a major human pathogen, and a leading cause of soft tissue and blood stream infections. One of the causes of its success as a pathogen is the peculiar array of immune evasion factors through which the bacterium avoids host defenses, where the staphylococcal protein A (SpA) plays a major role thanks to its IgG binding activities. Moreover, SpA has recently been proposed as a promising vaccine antigen. In this study, we evaluated the expression of SpA in a collection of staphylococcal strains, about 7% of which did not express SpA (SpA- strains), despite the presence of the gene. By a comparative genomic analysis, we identified that a mutation in the spa 5′ UTR sequence affecting the RBS is responsible for the loss of SpA in a subset of SpA- strains. Using a high-throughput qRT-PCR approach on a selected panel of virulence-related genes, we identified that the SpA- phenotype is associated with lower spa transcript levels and increased expression and production of capsule as well as other changes in the transcription of several key virulence factors. Our data suggest that the SpA- phenotype has occurred in geographically distinct strains through different molecular mechanisms including both mutation, leading likely to translation alterations, and transcriptional deregulation. Furthermore, we provide evidence that SpA- strains are highly susceptible to phagocytic uptake mediated by anti-capsule antibodies. These data suggest that S. aureus may alter its virulence factor expression pattern as an adaptation to the host or environment. Vaccination strategies targeting both SpA and capsule could therefore result in broader coverage against staphylococcal isolates than SpA alone

Th2 cells are less susceptible than Th1 cells to the suppressive activity of CD25+ regulatory thymocytes because of their responsiveness to different cytokines

AbstractT-cell clones generated from both CD4+CD25+ and CD8+CD25+ human thymocytes were assessed for their ability to suppress the proliferative response to allogeneic stimulation of type 1 T-helper (Th1) or type 2 T-helper (Th2) clones derived from autologous CD4+CD25- thymocytes. Both CD4+ and CD8+ T-regulatory (Treg) cells completely suppressed the proliferation of Th1 clones but exhibited significantly lower suppressive activity on the proliferation of Th2 clones. The partial suppressive effect on Th2 cells was further reduced by the addition in culture of interleukin-4 (IL-4), whereas it was increased in the presence of an anti–IL-4 monoclonal antibody (mAb). The suppressive activity on Th2 clones was also completely inhibited by the addition of IL-7, IL-9, and IL-15 but not of IL-2, whereas the suppressive effect on Th1 clones was only reverted by the addition of IL-15. Of note, Th2 clones expressed significantly higher amounts of mRNA for IL-4 receptor (IL-4R) and IL-9R α chains than Th1 clones, whereas the expression of mRNA for IL-2R, IL-7R, and IL-15R α chains was comparable. Taken together, these findings demonstrate that Th2 cells have a lower susceptibility than Th1 cells to the suppressive activity of human CD25+ regulatory thymocytes, because they are able to produce, and to respond to, growth factors distinct from IL-2, such as IL-4 and IL-9. (Blood. 2004; 103:3117-3121

Enhancing chestnut coppices: silvicultural management and socio-economic context.

 Castanea sativa is one of the most important species for timber production in Italy but, both management system, ownership type and wood chain structure, aren’t able to  enhance enough the market value of wood assortments. Although the high demand of quality timber, the internal production is heavily  reduced, mainly as far as timber quality is concerned and because of the lack of suitable timber sizes. In this context, experimental trials  have been approached to identify and verify which silvicultural methods are best suited to reach high yields depending to the investments  needed and the local socio-economical condition. Two technical approaches were evaluated: stand silviculture and single-tree oriented silviculture. As for the socio-economical aspects, a few demographic indexes have been examined and the first-phase processing enterprises  acting in the concerned area were analyzed. The goals of this paper are to evaluate the biological response to the applied silviculture, to  analyze the problems arisen and to estimate the applicability of the proposed methods in relation to the different socio-economic contexts. The research has been carried out in Tuscany in two important forest areas - Monte Amiata and Colline Metallifere - in young chestnut  coppices characterized by an homogeneous stand density and a good site index. The two examined districts showed some similarities  but they have mainly highlighted important differences about the social structure and concerns and enterprises characteristics. The area of Monte Amiata is typified by a higher residents density then the Colline Metallifere but only 1/3 of the population is employed in the agro-forest sector. In addition, in the Monte Amiata district most concerns are sized less than 2 hectares and chestnut is the main forest  species. On the contrary, in the Colline Metallifere the agro-forest sector (57% of workers) is one of the main sources of income for the  local communities and medium-sized concerns are noteworthy present. Chestnut stands have here a marginal role, oaks are dominant  and the prevailing assortment is firewood. From a silvicultural viewpoint, both the studied areas showed a quite good potentiality, suitabl