Focused examination of the intestinal lamina propria yields greater molecular insight into mechanisms underlying SIV induced immune dysfunction
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ABSTRACT:
ORGANISM(S): Macaca mulatta
PROVIDER: GSE34300 | GEO | 2011/12/10
SECONDARY ACCESSION(S): PRJNA151521
REPOSITORIES: GEO
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Project description:In this study three Indian rhesus macaques were infected with Simian Immunodeficiency Virus (SIVmac251). This generates a chronic infection mirroring AIDS in the animals. Prior to infection (day 0) and at two different time-points post-infection (day 21 and day 90), intestinal resection biopsies were performed. The intestinal tissue was then separated into different sub-sections including lamina-propria lymphocytes (LPL), intra-epithelial lymphocytes (IEL), stroma or matrix and epithelium. In this study we report the genome-wide transcriptional response at the two different time-points, specific to LPL, relative to pre-infection samples. For this purpose we have used the Affymetrix Rhesus Macaque GeneChip. 3 Rhesus Macaques prior to infection and 21 and 90 days of infection
2011-12-10 | E-GEOD-34300 | biostudies-arrayexpress
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2024-01-26 | PXD043704 | Pride
Project description:Immunization of macaques with simian immunodeficiency virus with deletions in nef (SIVΔnef) has been shown to elicit protective immunity to infection by pathogenic SIV, yet our understanding of the mechanisms that orchestrate protection and prevent pathogenesis remains limited. In the study, we utilize whole-genome transcriptional profiling to reveal molecular signatures of protective immunity in circulating CD8+ T cells of rhesus macaques vaccinated with SIVmac239Δnef and challenged with pathogenic SIVmac251. Microarrays were used to characterize changes in gene expression in blood CD8+ T cells that occur following vaccination of rhesus macaques with attenuated SIV∆nef and subsequent challenge with pathogenic SIVmac251, in comparison to corresponding changes in healthy controls and unvaccinated animals infected with pathogenic SIVmac251
2014-09-26 | GSE61766 | GEO
Project description:Immunization of macaques with simian immunodeficiency virus with deletions in nef (SIV?nef) has been shown to elicit protective immunity to infection by pathogenic SIV, yet our understanding of the mechanisms that orchestrate protection and prevent pathogenesis remains limited. In the study, we utilize whole-genome transcriptional profiling to reveal molecular signatures of protective immunity in circulating CD8+ T cells of rhesus macaques vaccinated with SIVmac239?nef and challenged with pathogenic SIVmac251. Microarrays were used to characterize changes in gene expression in blood CD8+ T cells that occur following vaccination of rhesus macaques with attenuated SIV?nef and subsequent challenge with pathogenic SIVmac251, in comparison to corresponding changes in healthy controls and unvaccinated animals infected with pathogenic SIVmac251 CD8+ T cells were isolated by magnetic beads from the blood of healthy uninfected macaques, macaques vaccinated with SIV?nef, and unvaccinated controls infected with SIVmac251, and used for RNA extraction and hybridization on Affymetrix microarrays. Blood samples from vaccinated animals were collected prior to vaccination, at 3, 20, and 40 weeks following vaccination. After the 40 week vaccination period, macaques were challenged with SIVmac251, and blood was again collected at 3 weeks following challenge. Blood was collected from the unvaccinated controls at 3 weeks following infection with SIVmac251
2014-09-26 | E-GEOD-61766 | biostudies-arrayexpress
Project description:We used the ileal loop model to assess the effects of enteric bacteria organisms on host gene expression in intestinal tissue independent of and following early SIV infection. SIV infection in the gut causes rapid and severe immune dysfunction and damage to the intestinal structure, this may alter the intimate interaction with lumenal organisms. This study was performed to determine whether early SIV infection, prior to the depletion of CD4+ T cells, can alter interaction of the host with pathogenic Salmonella serovar Typhimurium (ST) or commensal Lactobacillus plantarum (LP), and to further understand the earliest changes to the intestinal mucosa following SIV infection. We used microarray analysis to detail the global program of gene expression underlying changes in the ileum following early SIV infection, and if these changes in any way alter the host interaction/ response to pathogenic and commensal enteric bacteria. A subset of animals were infected with SIVmac251 for 2.5 days, following which they underwent a loop surgery where the ileum was sectioned off with surgical ties and bacteria (ST or LP) or their respective media controls (LB or MRS) were injected intralumenally. Following 5 hours of incubation the loops were excised and frozen. Tissue sections were cut and RNA extracted for gene expression analysis. Rhesus Macaques infected with SIVmac251 for 2.5 days compared to uninfected controls. Comparisons are of ileum loop sections injected with Salmonella serovar Typhimurium, Lactobacillus Plantarum or respective media controls LB or MRS.
2014-12-19 | E-GEOD-52589 | biostudies-arrayexpress
Project description:The intestinal mucosa harbors the largest accumulation of T lymphocytes in the body. While these T cells play an important role in immune homeostasis, they are also implicated in triggering and maintaining pathological intestinal inflammation. In humans they are poorly characterised, and even mouse transcriptomes have been reported for only a few individual cell types, many of which lack direct human equivalents. Using expression microarrays on T cells isolated from ileal biopsies and in silico analysis, we present here an unbiased, transcriptome-wide view of function in T cell subpopulations of the healthy human intestine and delineate signalling pathways that are distinct from those seen in peripheral blood T cells. Paired blood and intestinal biopsies from 6 age/sex matched healthy human subjects. Intestinal biopsies processed to release intraepithelial lymphocytes (IEL) and lamina propria lymphocytes (LPL). All samples then used to generate T effector memory (Tem) cells of CD4+ and CD8+ subsets by flow sorting. 6 individuals; 3 cell sources per individual (blood, LPL, IEL); 2 Tem subsets per cell source (CD4+ and CD8+). 36 arrays in total
2014-05-06 | E-GEOD-49877 | biostudies-arrayexpress
Project description:The objectives of this study were to determine the molecular mechanisms of host response during transition from primary to chronic SIV infection in the oral mucosa of rhesus macaques Transcriptioinal profiles were determined for 2 rhesus macaques infected for 6 wk with SIVmac251 and compared to profiles of 3 uninfected healthy controls
2009-01-12 | E-GEOD-14351 | biostudies-arrayexpress
Project description:Systemic vaccination with the attenuated virus SIVmac239-∆Nef provides sterilizing or partial protection to rhesus monkeys challenged with WT SIV strains, providing important opportunities to study key immunological components of a protective host response. Here we show that intravenous vaccination with SIVmac239-∆Nef provides two potentially crucial immunological barriers localized at mucosal surfaces that correlate with the vaccine’s protective effects against WT SIVmac251 vaginal challenge: 1) a conditioned and coordinated response from the mucosal epithelium that blunts the early inflammatory and chemotactic signalling cascade that aids virus propagation and expansion; 2) early on-site generation/diversification of SIV-specific Abs from ectopic germinal center-like lymphoid aggregates. This unique host response to WT SIVmac251 in the female reproductive tract of SIVmac239-∆Nef-vaccinated animals points to a multi-layered strategy for a protective host response during immunodeficiency virus exposure—rapid induction of humroal immunity at mucosal surfaces without the deleterious inflammatory side effects tied to innate recognition of virus. This vaccine-induced host response highlights potential key protective mechanisms needed for an effective HIV vaccine Total RNA was isolated from the cervix of 17 Indian Rhesus macaques (3 uninfected animals; 5 unvaccinated animals 4-5 days post vaginal exposure with SIVmac251; 4 SIVmac239-∆Nef-vaccinated animals before challenge; 5 SIVmac239-∆Nef-vaccinated animals 4-5 days post vaginal exposure with SIVmac251) and prepared for hybridization on Affymetrix GeneChip Rhesus Macaque Genome Arrays. Replicate arrays were performed for a number of the samples to minimize assay noise and significant host genes altered during virus exposure in female reproductive tract tissue were identified by their associated q-values (< 0.2) and fold change in expression (> 1.2).
2012-05-30 | E-GEOD-33251 | biostudies-arrayexpress
Project description:Recent studies of nonhuman primates (NHPs) have suggested that during the acute phase of infection, antiviral mucosal immunity is restricting viral replication in the primary infection compartment. These studies imply that HIV achieves systemic infection as a consequence of a failure in host antiviral immunity. Here, we used high-dose intrarectal inoculation of rhesus macaques with SIVmac251 to examine how the mucosal immune system is overcome by SIV during acute infection. The host response in rectal mucosa was characterized by mRNA deep sequencing (mRNA-seq) at 3 and 12 days post inoculation (DPI) in 4 animals for each time point. The eight RMs were intrarectally challenged with SIVmac251 using 1 mL of a high-dose inoculum (6000 TCID50/mL). SIV inoculates were deposited at a rectal depth of 25 mm from the anus. Baseline rectal samples were obtained 14 days prior to viral challenge by pinch biopsy.
2014-04-17 | E-GEOD-56845 | biostudies-arrayexpress
Project description:The study describes miRNA expression in intact duodenum following chronic delta 9 tetrahydrocannabinol (M-NM-^T9-THC) administration to SIV-infected rhesus macaques. Chronic M-NM-^T9-THC administration to uninfected macaques significantly and positively modulated intestinal miRNA expression by increasing the total number of differentially expressed miRNAs from 14 to 60 days post infection (DPI). At 60DPI, ~28% of miRNAs showed decreased expression in VEH/SIV compared to none in the THC/SIV group. Furthermore, compared to the VEH/SIV group, THC selectively upregulated the expression of miR-10a, miR-24, miR-99b, miR-145, miR-149 and miR-187 previously shown to target proinflammatory molecules. NOX4, a potent reactive oxygen species generator was confirmed as a direct miR-99b target. A significant increase in NOX4+ crypt epithelial cells was detected in VEH/SIV compared to the THC/SIV group. We speculate that miR-99b-mediated NOX4 downregulation may protect the intestinal epithelium from oxidative stress-induced damage. Twelve age and weight matched male Indian rhesus macaques were randomly divided into 4 groups. Group 1 (n=1) received vehicle (1:1:18 of emulphor : alcohol : saline) and no infection. Group 2 (THC only, n=3) animals received twice daily intramuscular injections of M-NM-^T9-THC and no infection. Group-3 THC/SIV, (n=4) animals received twice daily injections of vehicle and were infected intravenously with 100TCID50 of SIVmac251. Group-4 (VEH/SIV, n=4) animals received twice daily injections of M-NM-^T9-THC similar to group 1 for four weeks prior to SIV infection. Duodenal pinch biopsies were collected before infection and thereafter at 14 and 30 days post infection. All animals were necropsied at 60 days post SIV infection. ~100 ng of total RNA was first reverse transcribed and preamplified according to the manufacturerM-bM-^@M-^Ys recommendation. microRNA expression profiling was performed using TaqMan M-BM-.OpenArrayM-BM-. Human microRNA panels. Data analysis was performed using ExpressionSuiteM-BM-. software. Data was normalized to three endogenous controls (RNU44, RNU48 and snoU6). Delta CT values were calculated by subtracting individual miRNA CT values from an average of all three endogenous controls. Comparisons were made between preinfection and all three treatment groups at 14, 30 and 60 DPI. To determine the effect of chronic THC treatment during SIV infection, comparisons were also made between VEH/SIV and THC/SIV at all three time points.
2014-11-19 | E-GEOD-61654 | biostudies-arrayexpress