Infected site-restricted Foxp3+ natural regulatory T cells are specific for microbial antigens

Natural regulatory T (T reg) cells are involved in control of the immune response, including response to pathogens. Previous work has demonstrated that the repertoire of natural T reg cells may be biased toward self-antigen recognition. Whether they also recognize foreign antigens and how this recognition contributes to their function remain unknown. Our studies addressed the antigenic specificity of natural T reg cells that accumulate at sites of chronic infection with Leishmania major in mice. Our results support the idea that natural T reg cells are able to respond specifically to foreign antigens in that they strongly proliferate in response to Leishmania-infected dendritic cells, they maintain Foxp3 expression, and Leishmania-specific T reg cell lines can be generated from infected mice. Surprisingly, the majority of natural T reg cells at the infected site are Leishmania specific. Further, we showed that parasite-specific natural T reg cells are restricted to sites of infection and that their survival is strictly dependent on parasite persistence

Acute mucosal pathogenesis of feline immunodeficiency virus is independent of viral dose in vaginally infected cats

<p>Abstract</p> <p>Background</p> <p>The mucosal pathogenesis of HIV has been shown to be an important feature of infection and disease progression. HIV-1 infection causes depletion of intestinal lamina propria CD4+ T cells (LPL), therefore, intestinal CD4+ T cell preservation may be a useful correlate of protection in evaluating vaccine candidates. Vaccine studies employing the cat/FIV and macaque/SIV models frequently use high doses of parenterally administered challenge virus to ensure high plasma viremia in control animals. However, it is unclear if loss of mucosal T cells would occur regardless of initial viral inoculum dose. The objective of this study was to determine the acute effect of viral dose on mucosal leukocytes and associated innate and adaptive immune responses.</p> <p>Results</p> <p>Cats were vaginally inoculated with a high, middle or low dose of cell-associated and cell-free FIV. PBMC, serum and plasma were assessed every two weeks with tissues assessed eight weeks following infection. We found that irrespective of mucosally administered viral dose, FIV infection was induced in all cats. However, viremia was present in only half of the cats, and viral dose was unrelated to the development of viremia. Importantly, regardless of viral dose, all cats experienced significant losses of intestinal CD4+ LPL and CD8+ intraepithelial lymphocytes (IEL). Innate immune responses by CD56+CD3- NK cells correlated with aviremia and apparent occult infection but did not protect mucosal T cells. CD4+ and CD8+ T cells in viremic cats were more likely to produce cytokines in response to Gag stimulation, whereas aviremic cats T cells tended to produce cytokines in response to Env stimulation. However, while cell-mediated immune responses in aviremic cats may have helped reduce viral replication, they could not be correlated to the levels of viremia. Robust production of anti-FIV antibodies was positively correlated with the magnitude of viremia.</p> <p>Conclusions</p> <p>Our results indicate that mucosal immune pathogenesis could be used as a rapid indicator of vaccine success or failure when combined with a physiologically relevant low dose mucosal challenge. We also show that innate immune responses may play an important role in controlling viral replication following acute mucosal infection, which has not been previously identified.</p

European soybean to benefit people and the environment.

Europe imports large amounts of soybean that are predominantly used for livestock feed, mainly sourced from Brazil, USA and Argentina. In addition, the demand for GM-free soybean for human consumption is project to increase. Soybean has higher protein quality and digestibility than other legumes, along with high concentrations of isoflavones, phytosterols and minerals that enhance the nutritional value as a human food ingredient. Here, we examine the potential to increase soybean production across Europe for livestock feed and direct human consumption, and review possible effects on the environment and human health. Simulations and field data indicate rainfed soybean yields of 3.1 ± 1.2 t ha-1 from southern UK through to southern Europe (compared to a 3.5 t ha-1 average from North America). Drought-prone southern regions and cooler northern regions require breeding to incorporate stress-tolerance traits. Literature synthesized in this work evidenced soybean properties important to human nutrition, health, and traits related to food processing compared to alternative protein sources. While acknowledging the uncertainties inherent in any modelling exercise, our findings suggest that further integrating soybean into European agriculture could reduce GHG emissions by 37-291 Mt CO2e year-1 and fertiliser N use by 0.6-1.2 Mt year-1, concurrently improving human health and nutrition

Postmarket surveillance of 3D-printed implants for sacroiliac joint fusion

Daniel Cher,1 Kendrick Wroe,2 W Carlton Reckling,3 Scott Yerby4 1Clinical Affairs, SI-BONE, Inc., Santa Clara, CA, USA; 2Quality Assurance, SI-BONE, Inc., Santa Clara, CA, USA; 3Medical Affairs, SI-BONE, Inc., Santa Clara, CA, USA; 4Research and Development, SI-BONE, Inc., Santa Clara, CA, USA Background: Government regulations require postmarket surveillance for cleared/approved medical devices. Trend analysis of newly marketed devices may help to confirm device-related safety or uncover other device or procedure-related problems. Methods: Complaints related to the use of 3D-printed triangular titanium implants for sacroiliac joint (SIJ) fusion were compared with those of the prior machined version of the device manufactured with a titanium plasma spray (TPS) coating. Event rates were calculated either by dividing event counts by numbers of surgeries or, for late events, using Kaplan&ndash;Meier survival analysis. Results: Three types of complaints with nontrial frequencies were identified. Issues in instruments occurred at a low and constant rate (1.3%). Using Kaplan&ndash;Meier analysis, pain-related complaints occurred at a low and similar rate in both groups (&lt;0.5%). The 1-year cumulative probability of surgical revision was low in both the 3D and machined versions of the device (1.5% for machined and 1% for 3D printed, P=0.0408 for difference). No implant breakages or migrations were identified in either group, and overall rates were similar to a previously published report. Conclusion: The 3D-printed version of triangular titanium implant was associated with complaint and adverse event rates similar to those for the prior machined version of the device. Keywords: permanent implants, quality system, complaint analysis, adverse events, postmarket surveillance, sacroiliac joint fusio