Activity

Interleukin 8 (IL8) is a major mediator of the innate immune response. Polymorphisms in this gene are associated with susceptibility to inflammatory disease in humans. Two major promoter polymorphic haplotypes (IL8-h1 and IL8-h2) segregating in cattle populations have shown a significant effect on the immune response profile in calves but their implications for transition cow immunity have not been established. The aims of this study were to assess functional relevance of the IL8 haplotypes on the immunological traits of periparturient cows (n = 32) belonging to three genetic groups Holstein (HO), Simmental (SI) and their crosses (CR) and to evaluate the frequency of IL8 haplotypes in the HO (dairy) and SI (dual purpose) pure breeds. IL8 haplotypes showed a significant effect on circulating number of both T helper lymphocytes (P = 0.0133) and T cytotoxic lymphocytes (P = 0.0024). Differences in percentage of CD14+ monocytes and T lymphocyte subsets were found between haplotype groups at different time points. Plasma concentrations of Serum Amyloid A (SAA) and Haptoglobin (Hp) were enhanced at calving in IL8-h2 (P = 0.0019, P = 0.0029) and IL8-het (P = 0.050 and P = 0.052) respectively, compared with IL8-h1 cows. In contrast, significantly lower levels of reactive oxygen metabolites (d-ROMs) activation were identified in IL8-h2 and IL8-het cows after calving compared with IL8-h1 cows. Furthermore, genotyping results showed that SI cows have a high frequency of the homozygous IL8-h2 haplotype compared to the HO cows (87.5 % vs 40 %) which reflects the different selective pressure between the two pure breeds. In conclusion, our preliminary data suggests that IL8 promoter haplotype is associated with significant and dynamic changes in immunological traits during peripartum and early lactation period. Future work will focus on a more comprehensive assessment of immune changes in additional cows.An important strategy to reduce the risk of visceral leishmaniasis (VL) in humans is to control the infection and disease progression in dogs, the domestic reservoir of Leishmania infantum parasites. Androgen Receptor Antagonist Certain therapeutic strategies that modulate the host immune response show great potential for the treatment of experimental VL, restoring the impaired effector functions or decreasing host excessive responses. It is known that the overproduction of interleukin-10 (IL-10) promotes parasite replication and disease progression in human VL as well as in canine visceral leishmaniasis (CVL). Thus, in the present study we investigated the potential of the anti-canine IL-10 receptor-blocking monoclonal antibody (Bloq IL-10R) to control and reduce in vitro infectivity of L. infantum and improve the ability of PBMC isolated from VL dogs to alter the lymphoproliferative response and intracytoplasmic cytokines. Overall, GFP+Leishmania showed lower capacity of in vitro infectivity in the presence of Bloq IL-10R. Moreover, addition of Bloq IL-10R in cultured PBMC enhanced T-CD4 and CD8 proliferative response and altered the intracytoplasmic cytokine synthesis, reducing CD4+IL-4+ cells and increasing CD8+IFN-γ+ cells after specific antigen stimulation in PBMC of dogs. Furthermore, we observed an increase of TNF-α levels in supernatant of cultured PBMC under IL-10R neutralizing conditions. Together, our findings are encouraging and reaffirm an important factor that could influence the effectiveness of immune modulation in dogs with VL and suggest that blocking IL-10R activity has the potential to be a useful approach to CVL treatment.

To investigate the influence of tolerance dendritic cells (tolDCs), generated from Bone marrow mesenchymal stem cells (BM-MSCs) treated with rapamycin (Rapa) on liver allograft survival in a rat acute liver transplantation model.

Different GM-CSF induction project was used to obtain immature DCs (imDCs), mature DCs (matDCs) or tolDCs from BM-MSCs. First, MLR was performed to analyze the activity of tolDCs on polyclonaly stimulated total T cells. Then, co-cultured imDCs, matDCs and tolDCs with CD8

T cells isolated by magnetic activated cell sorting to analyze the influence on its regulatory characteristic. Last, the established rat acute liver transplantation model were adoptive transfused with imDCs, matDCs or tolDCs isolated by anti-CD11c immunomagnetic beads. The phenotype of DC cells and level of CD8

Treg in the culture system and in vivo, the expression of CD8 and CD45RC in the tissues were analyzed by flow cytometry and immunohistochemistry, respectively.

The loGM-CSF plus IL-4 decreased the cost by rat that per-infused with matDCs and imDCs, respectively.

Rapa modified tolDCs derived from BM-MSCs reversed graft rejection by improve tolerance characteristics of CD8

CD45RC

Treg in acute liver rat transplantation.

Rapa modified tolDCs derived from BM-MSCs reversed graft rejection by improve tolerance characteristics of CD8+CD45RC-Treg in acute liver rat transplantation.Short-term imbalances of dietary nutrients occur during natural fluctuations in roughage quality (e.g. on pasture) or temporal shortages of supplementary feed components. In contrast to a deficiency, macronutrients (i.e. carbohydrates, proteins, lipids) beyond the adequate supply with other nutrients may, for instance, alter milk composition, increase BW or result in a greater excretion of nitrogen. Especially dairy cows with a moderate performance, in mid- or late lactation, or in extensive farming systems may be exposed to imbalanced rations. A better understanding of metabolic and endocrine responses depending on macronutrient supply may help to precisely feed dairy cows. The present study investigated short-term metabolic and endocrine responses to different levels of concentrates formulated to particularly provide one major macronutrient source (carbohydrates, proteins or lipids). Based on parity number, lactational stage, milk yield and BW, nine mid-lactating cows (211 ± 19 days in milk) were grouped ind with the glucogenic concentrate. Milk and plasma urea concentrations were elevated in the aminogenic and to a lesser extent in the lipogenic treatment compared with the glucogenic treatment. Glucose concentrations in plasma were not affected by treatments, whereas insulin and glucagon increased, and NEFA concentrations decreased only in cows fed 7.5 kg/d aminogenic concentrate compared with the glucogenic and lipogenic treatment. Activities of ASAT, GGT and GLDH as well as the total antioxidant capacity were not affected by diets. In conclusion, immediate metabolic and endocrine responses were observed due to the short-term dietary changes. Particularly, a surplus of nitrogen supply via the aminogenic diet affected metabolic responses and stimulated insulin and glucagon secretion.