Two distinct populations of Bovine IL-17+ T-cells can be induced and WC1+IL-17+γδ T-cells are effective killers of protozoan parasites

IL-17 has emerged as a key player in the immune system, exhibiting roles in protection from infectious diseases and promoting inflammation in autoimmunity. Initially thought to be CD4 T-cell-derived, the sources of IL-17 are now known to be varied and belong to both the innate and adaptive arms of the immune system. Mechanisms for inducing IL-17 production in lymphoid cells are thought to rely on appropriate antigenic stimulation in the context of TGF-β1, IL-6 and/or IL-1β. Using culture protocols adapted from human studies, we have effectively induced both bovine CD4+ and WC1+ γδ T-cells to produce IL-17 termed Th17 and γδ17 cells, respectively. The negative regulatory effect of IFN-γ on mouse and human IL-17 production can be extended to the bovine model, as addition of IFN-γ decreases IL-17 production in both cell types. Furthermore we show that infection with the protozoan Neospora caninum will induce fibroblasts to secrete pro-IL-17 factors thereby inducing a γδ17 phenotype that preferentially kills infected target cells. Our study identifies two T-cell sources of IL-17, and is the first to demonstrate a protective effect of IL-17+ T-cells in ruminants. Our findings offer further opportunities for future adjuvants or vaccines which could benefit from inducing these responses

Malignant Catarrhal Fever Induced by Alcelaphine herpesvirus 1 Is Associated with Proliferation of CD8+ T Cells Supporting a Latent Infection

Alcelaphine herpesvirus 1 (AlHV-1), carried by wildebeest asymptomatically, causes malignant catarrhal fever (WD-MCF) when cross-species transmitted to a variety of susceptible species of the Artiodactyla order. Experimentally, WD-MCF can be induced in rabbits. The lesions observed are very similar to those described in natural host species. Here, we used the rabbit model and in vivo 5-Bromo-2′-Deoxyuridine (BrdU) incorporation to study WD-MCF pathogenesis. The results obtained can be summarized as follows. (i) AlHV-1 infection induces CD8+ T cell proliferation detectable as early as 15 days post-inoculation. (ii) While the viral load in peripheral blood mononuclear cells remains below the detection level during most of the incubation period, it increases drastically few days before death. At that time, at least 10% of CD8+ cells carry the viral genome; while CD11b+, IgM+ and CD4+ cells do not. (iii) RT-PCR analyses of mononuclear cells isolated from the spleen and the popliteal lymph node of infected rabbits revealed no expression of ORF25 and ORF9, low or no expression of ORF50, and high or no expression of ORF73. Based on these data, we propose a new model for the pathogenesis of WD-MCF. This model relies on proliferation of infected CD8+ cells supporting a predominantly latent infection

Peripheral and placental immune responses in sheep after experimental infection with "Toxoplasma gondii" at the three terms of gestation

P. 1-9Although it is known that gestation could infuence the clinical course of ovine toxoplasmosis, the precise efect of the term of gestation when sheep are infected are yet mostly unknown. The aim of this study was to evaluate the peripheral and placental immune responses developed in pregnant sheep after experimental infection with Toxoplasma gondiiat diferent times of gestation. Thirty‑six pregnant sheep were allocated in diferent groups, orally inocu‑lated with sporulated oocysts of T. gondiiat early, mid and late gestation and culled within 30 days post‑infection. The peripheral humoral and cytokine responses were evaluated, as well as the transcription of cytokines at the placenta. Serological analysis revealed that, regardless the term of gestation when infected, specifc IgG against T. gondiiwere detected from day 8 post‑infection and there was an early peripheral release of IFN‑γ at the frst week post‑infection followed by a short peak of IL10 and TNF‑α at the second week post‑infection. There were no signifcant diferences in this response between infected groups. At the placenta, a similar increase in transcription of IFN‑γ, and TNF‑α was found at the three terms of gestation, while IL‑4 increased mainly at the frst and second terms and IL‑10 transcription was higher at the last term. While these fndings show that both Th1 and Th2 cytokines play a key role in the patho‑genesis of ovine toxoplasmosis and that placental and peripheral immune responses do not closely correlate, there seems to be no clear modulation of these responses along the gestation.S

Cytokine Gene Expression in the Maternal-Fetal Interface in Somatic Cell Nuclear Transfer Pregnancies in Small Ruminants

The present retrospective study investigates pregnancy rates, incidence of pregnancy losses and large offspring syndrome (LOS), and immune-related gene expression of sheep and goat somatic cell nuclear transfer (SCNT) pregnancies. We hypothesized that significantly higher pregnancy losses observed in sheep SCNT pregnancies compared to goats are due to the increased amounts of T-helper 1 cytokines and pro-inflammatory mediators at the maternal-fetal interface. Sheep and goat SCNT pregnancies were generated using the same procedure. Control pregnancies were established by natural breeding. Although SCNT pregnancy rates at 45 days were similar in both species, pregnancy losses between 45 and 60 days and incidence of LOS were significantly increased in sheep compared with goats. At term, the expression of pro-inflammatory genes in sheep SCNT placentas was increased while the one of goat SCNT was similar to the control animals. Among the genes that had altered expression in sheep SCNT placentas are CTLA4, IL2RA, CD28, IFNG, IL6, IL10, TGFB1, TNF, IL1A and CXCL8. MHC-I protein expression was greater in sheep and goat SCNT placentas at term compared with control pregnancies. An unfavorable immune environment is present at the maternal-fetal interface in sheep SCNT pregnancies

The influence of solid state information and descriptor selection on statistical models of temperature dependent aqueous solubility.

Predicting the equilibrium solubility of organic, crystalline materials at all relevant temperatures is crucial to the digital design of manufacturing unit operations in the chemical industries. The work reported in our current publication builds upon the limited number of recently published quantitative structure-property relationship studies which modelled the temperature dependence of aqueous solubility. One set of models was built to directly predict temperature dependent solubility, including for materials with no solubility data at any temperature. We propose that a modified cross-validation protocol is required to evaluate these models. Another set of models was built to predict the related enthalpy of solution term, which can be used to estimate solubility at one temperature based upon solubility data for the same material at another temperature. We investigated whether various kinds of solid state descriptors improved the models obtained with a variety of molecular descriptor combinations: lattice energies or 3D descriptors calculated from crystal structures or melting point data. We found that none of these greatly improved the best direct predictions of temperature dependent solubility or the related enthalpy of solution endpoint. This finding is surprising because the importance of the solid state contribution to both endpoints is clear. We suggest our findings may, in part, reflect limitations in the descriptors calculated from crystal structures and, more generally, the limited availability of polymorph specific data. We present curated temperature dependent solubility and enthalpy of solution datasets, integrated with molecular and crystal structures, for future investigations

The extent of parasite-associated necrosis in the placenta and foetal tissues of cattle following Neospora caninum infection in early and late gestation correlates with foetal death

The protozoan parasite Neospora caninum is the most frequently diagnosed abortifacient in the UK and a leading cause of abortion worldwide but the mechanisms leading to abortion are not fully understood. The distribution of parasites and the histopathological changes in the placenta and foetus were compared in 12 cows following experimental infection of cattle with N. caninum in early (n = 6) and late (n = 6) gestation, by PCR, immunohistology, light microscopy and transmission electron microscopy. Twelve uninfected pregnant cattle were used as controls. Infection in early gestation led to foetal death. In the placentae of cattle immediately following foetal death, N. caninum DNA was detected and there was evidence of widespread parasite dissemination. This was associated with extensive focal epithelial necrosis, serum leakage and moderate maternal interstitial mononuclear cell infiltration. In the foetuses, parasites were evident in all tissues examined and were associated with necrosis. In the placenta of cattle infected in late gestation, N. caninum DNA was detected sporadically but parasites were not evident immunohistologically. Small foci of necrosis were seen associated with mild interstitial mononuclear cell infiltration. Detection of N. caninum DNA in the foetuses was sporadic and parasites were demonstrated immunohistologically in brain and spinal cord only, with an associated mononuclear cell infiltration. This data is consistent with uncontrolled parasite spread in an immunologically immature foetus and could, via multiparenchymal necrosis of foetal tissues or the widespread necrosis and inflammation observed in the placenta, be the cause of Neospora-associated abortions. (C) 2007 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved