Project description:This SuperSeries is composed of the following subset Series: GSE23859: Regional Immune Response to Trichostrongylis colubriformis - Gene Expression during the Development of Immunity GSE23863: Regional Immune Response to Trichostrongylis colubriformis - Gene Expression during Challenge of Immunized Sheep Refer to individual Series
Project description:Once Haemonchus contortus infects sheep it receives a series of host attacks, especially those relating to the infected animal’s T lymphocytes immune response. To obtain a systematic genome-wide profiling of the T lymphocyte genes involved, microarrays were used to compare gene expression between 0 days post infection (dpi), 3-5 dpi, 25-30 dpi and 60dpi in infected sheep. In this 853, 242 and 42 differentially expressed genes were acquired in the 3d vs. 0d comparison, the 30d vs. 0d comparison and the 60d vs. 0d comparison, respectively. Gene Ontology and pathway analysis indicated that modulated genes including SUGT1, FCER1G, CD23, IL-13 and galectin-14, were mostly associated with cellular homeostasis maintaining and immune response. Haemonchus contortus infection induced gene expression in sheep T lymphocytes was measured at 0, 3, 30 and 60 days post infection. Four time-series experiments were performed at each sheep (2#, 3# and 5#).
Project description:Infection of sheep with Brucella ovis results in ovine brucellosis, a disease characterized by infertility in rams, abortion in ewes and increased perinatal mortality in lambs. During the course of the infection both the ovine immune response and host cell gene expression are modified. The objective of this research was to conduct a preliminary characterization of differential gene expression in rams experimentally infected with B. ovis by microarray hybridization and real-time RT-PCR. Six hybridizations were conducted using total RNA from three individual infected sheep at 15 and 60 days post infection. In each comparison, the control channels contained total RNA from each of the same three sheep at 0 days post infection. Ratios were calculated as B. ovis-infected sheep at 15 and 60 dpc versus uninfected animals at 0 dpc.
Project description:Our objective was to investigate differences in gene expression between 24 parasite-resistant hair and 24 susceptible wool lambs to determine genetic mechanisms involved in resistance to H. contortus. Half of the animals of each breed were infected and sacrificed at 3 or 27 days post-infection; the remaining animals were uninfected controls. Breed differences in abomasum and abomasal lymph node tissue gene expression were assessed using bovine cDNA microarrays. Over 60 transcripts differed between breeds for each tissue and infection status. Genes differentially expressed between hair and wool sheep 3 days PI were assessed for gene function and mechanisms for greater immune cell infiltration, abomasal tissue repair, Th17 response, and anticoagulation were present in parasite-resistant hair sheep. By 27 days PI, hair sheep had greater expression of genes involved in gut motility, inflammatory cytokines, and cell proliferation and differentiation compared to wool sheep. Changes in these processes indicate Caribbean hair sheep have a stronger inflammatory response when infected with H. contortus which may facilitate the increased parasite resistance observed in these sheep.
Project description:we constructed a methylated DNA immunoprecipitation combined with high throughput sequencing (MeDIP-seq) strategy to investigate the differentially methylated genes between the Dorset, HanBB and Han++ sheep ovaries. Our findings suggest the genes involved in immune response, branched-chain amino acid metabolism, cell growth and cell junction were differentially methylated in or around the gene body regions. These findings provide prospective insights on the epigenetic basis of sheep fecundity.
Project description:Understanding the way in which the airway heals in response to injury is fundamental to dissecting the mechanisms underlying airway disease pathology. Only limited data is available in relation to in vivo characterisation of the molecular features of repair in the airway. This study sought to characterise the dynamic changes in gene expression that are associated with airway repair in response to physical injury. Gene expression changes in the airway wall following bronchial brush biopsy were profiled in anaesthetised sheep. The experimental design featured sequential studies in the same animals (n=8) over the course of a week and yielded data relating to the repair process at 6 hours, and 1, 3 and 7 days after injury. Notable features of the transcriptional response included the early and sustained preponderance of down-regulated genes associated with angiogenesis and immune cell activation, selection and differentiation. Later features of the repair response included the up-regulation of cell cycle genes at d1 and d3, and the later pronounced up-regulation of extracellular matrix-related genes at d3 and d7. It is possible to follow the process of airway wall repair in response to physical injury in the same animal over the course of time. Transcriptional changes featured coordinate expression of functionally related genes in a reproducible manner both within and between animals. This characterisation will provide a foundation against which to assess the perturbations that accompany airway disease pathologies of comparative relevance. Keywords: response to airway injury Each sheep was subjected to a protocol which involved the procedure of endobronchial brush biopsy (BBr) being performed, under anaesthesia, on three occasions, with two separate airway sites being subjected to brushing on each occasion. Two sheep were subjected to BBr seven days, three days and six hours prior to euthanasia, two sheep at seven days, three days and one day prior to euthanasia, two sheep at seven days, one day and six hours prior to euthanasia and two sheep at three days, one day and six hours prior to euthanasia. At post mortem examination (PME) each time point was therefore represented by material derived from six sheep. Airway tissue from a naM-CM-/ve site (from a segment not subjected to BBr) was also collected from each sheep at necropsy.
Project description:Despite the promise of immune checkpoint inhibition (ICI), therapeutic responses remain limited. This raises the possibility that standard of care treatments delivered in concert may compromise the tumor response. To address this, we employed tobacco-signature HNSCC murine models in which we mapped tumor-draining lymphatics and developed models for regional lymphablation with surgery or radiation. Remarkably, we found that lymphablation eliminates the tumor ICI response, significantly worsening overall survival and repolarizing the tumor- and peripheral- immune compartments. Mechanistically, within tumor-draining lymphatics, we observed an upregulation of cDC1 cells and IFN-I signaling and show that both are necessary for the ICI response and lost with lymphablation. Ultimately, we provide a mechanistic understanding of how standard oncologic therapies targeting regional lymphatics impact the tumor response to immune- oncology therapy in order to define rational, lymphatic-preserving treatment sequences that mobilize systemic antitumor immunity, achieve optimal tumor responses, control regional metastatic disease, and confer durable antitumor immunity.