Dendritic Cell-Mediated-Immunization with Xenogenic PrP and Adenoviral Vectors Breaks Tolerance and Prolongs Mice Survival against Experimental Scrapie

In prion diseases, PrPc, a widely expressed protein, is transformed into a pathogenic form called PrPSc, which is in itself infectious. Antibodies directed against PrPc have been shown to inhibit PrPc to PrPSc conversion in vitro and protect in vivo from disease. Other effectors with potential to eliminate PrPSc-producing cells are cytotoxic T cells directed against PrP-derived peptides but their ability to protect or to induce deleterious autoimmune reactions is not known. The natural tolerance to PrPc makes difficult to raise efficient adaptive responses. To break tolerance, adenovirus (Ad) encoding human PrP (hPrP) or control Ad were administered to wild-type mice by direct injection or by transfer of Ad-transduced dendritic cells (DCs). Control Ad-transduced DCs from Tg650 mice overexpressing hPrP were also used for immunization. DC-mediated but not direct administration of AdhPrP elicited antibodies that bound to murine native PrPc. Frequencies of PrP-specific IFNγ-secreting T cells were low and in vivo lytic activity only targeted cells strongly expressing hPrP. Immunohistochemical analysis revealed that CD3+ T cell infiltration was similar in the brain of vaccinated and unvaccinated 139A-infected mice suggesting the absence of autoimmune reactions. Early splenic PrPSc replication was strongly inhibited ten weeks post infection and mean survival time prolonged from 209 days in untreated 139A-infected mice to 246 days in mice vaccinated with DCs expressing the hPrP. The efficacy appeared to be associated with antibody but not with cytotoxic cell-mediated PrP-specific responses

T Cells Kill Bacteria Captured by Transinfection from Dendritic Cells and Confer Protection in Mice

During infections, dendritic cells DCs phagocytose, process and present bacterial antigens to the T lymphocytes, thus triggering the adaptive immunity. In vivo, bacteria can be found inside antigen presenting cells APCs and lymphocytes, however, how bacteria invade T cells remains unknown. Here we show that T cells take up bacteria from infected DCs in a process remarkably enhanced by antigen recognition herein called trans infection. Strikingly, trans infected T cells efficiently eliminate the bacteria acquired from the infected DCs within the first hours after trans infection. Moreover, trans infected T cells produced high levels of pro inflammatory cytokines and were able to protect mice from bacterial challenge after adoptive transfer. Our data, therefore, show that T lymphocytes resemble to cells of the innate immune system in the sense that they are able to engulf and kill bacteria demonstrating novel and unexpected roles for T lymphocytes during bacterial clearanc

Maternal distress and the development of hypertensive disorders of pregnancy

Despite the implementation of programmes to improve maternal health, maternal and foetal mortality rates still remain high. The presence of maternal distress and its association with the development of pregnancy hypertensive disorders is not well established. The aim of this study was to evaluate the association between maternal distress and the development of hypertensive disorders in pregnancy in a prospective cohort of 321 Mexican women. Symptoms of maternal distressing were evaluated at week 20th of gestation using the General Health Questionnaire. The presence of acute somatic symptoms, social dysfunction, anxiety and insomnia increased the odds of developing a pregnancy hypertensive disorder by 5.1–26.4 times in study population (p values < .05). Our results support the participation of maternal distress in the development of hypertensive disorders of pregnancy. The implementation of effective programmes prioritising risk factors during pregnancy including the presence of maternal distressing factors is recommended.Impact statement What is already known on this subject: Changes in the nervous, endocrine, and immune systems have been observed in pregnant women with distress conditions leading to gestational disorders. What do the results of this study add: The presence of acute somatic symptoms, social dysfunction, anxiety and insomnia increased the developing of hypertensive disorders in Mexican population. What are the implications of these findings for clinical practice and/or further research: These findings may contribute to a better understanding of the role of the maternal stress in the development of hypertensive disorders of pregnancy, and in the implementation of effective programmes for clinical practice prioritising risk factors during pregnancy, including the presence of maternal distressing factors

Density and habitat prefereces of male little bustard across contrasting agro-pastoral landscapes in Sardinia (Italy)

The little bustard Tetrax tetrax has undergone severe range contraction within Europe due to abandonment of traditional agro-pastoral activities. Previous studies of habitat selection have mainly focused on extensive cereal and cropland mosaics, while the species’ ecology in pastoral landscapes is understood less well, and data are completely lacking from the Sardinian population. We conducted distance sampling surveys of displaying males across three contrasting landscapes in Sardinia and modelled habitat preference at both the landscape and local (within pastures and recent fallows) scale. Abbasanta, with a balance of pasture and cropland, the greatest isolation from roads and shortest vegetation, supported the highest little bustard densities (95%CI 2.7–3.4 males/100 ha). Significantly lower densities were found in two landscapes with lower isolation from roads and taller vegetation within grasslands: Campeda (0.1–0.2 males/100 ha), comprising cropland and pasture in similar proportions to those found at Abbasanta, and Campidano (0.3–0.4 males/100 ha) that was dominated by cereal agriculture. At the landscape level, males preferred pastures and recent fallows over arable lands. At the local scale, within grasslands, probability of occurrence was greater with shorter vegetation, more legume and green herb cover and at points remote from roads. Shorter vegetation in grasslands resulted from high grazing pressure, and habitat suitability for breeding males depends strongly on extensively grazed grasslands. Conservation efforts for this species should focus on maintaining traditional agro-pastoral practices which maintain large areas of extensively grazed pastures and recent fallows located far from roads