Salmonella enterica serotype Typhimurium causes an acute inflammatory reaction in the cecum of streptomycin pre-treated mice. We determined global changes in gene expression elicited by serotype Typhimurium in the cecal mucosa. The gene expression profile was dominated by T cell derived cytokines and genes whose expression is known to be induced by these cytokines. Markedly increased mRNA levels of interferon (IFN-gamma), interleukin-22 (IL-22) and IL-17 were detected by quantitative real-time PCR. Furthermore, mRNA levels of genes whose expression is induced by IFN-gamma, IL-22 or IL-17, including macrophage inflammatory protein 2 (MIP-2), inducible nitric oxide synthase (Nos2), lipocalin-2, MIP-1alpha, MIP-1beta, and keratinocyte-derived cytokine (KC), were also markedly increased. To assess the importance of T cells in orchestrating this pro-inflammatory gene expression profile, we depleted T cells using a monoclonal antibody prior to investigating cecal inflammation caused by serotype Typhimurium in streptomycin pre-treated mice. Depletion of CD3+ T cells resulted in a dramatic reduction in gross pathology, a significantly reduced recruitment of neutrophils and a marked reduction in mRNA levels of IFN-gamma, IL-22, IL-17, iNOS, lipocalin-2 and KC. Our results suggest that T cells play an important role in amplifying inflammatory responses induced by serotype Typhimurium in the cecal mucosa.
T cells help to amplify inflammatory responses induced by Salmonella enterica serotype Typhimurium in the intestinal mucosa.
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View SamplesTo understand the role of MiT in Drosophila, we set out to identify critical gene targets by looking at changes in the WT transcriptome induced by either gain or loss of MiT function. Mutant hindgut and malpighian tubules provided loss-of function tissue and nub-Gal4-driven expression of MiT in the wing epithelium was used for gain-of-function. In the wing disc experiment, 543 genes were upregulated by exogenous MiT, and 359 genes were downregulated (>1.4 fold; P value < 0.01). In the larval HG+MT, 897 genes were downregulated and 898 were upregulated (>1.4 fold; P value < 0.01) after MiT. Among these genes, 85 were both upregulated in wing discs and downregulated in mutant HG+MT, and are the common genes that regulated by MiT in both tissues.
Mitf is a master regulator of the v-ATPase, forming a control module for cellular homeostasis with v-ATPase and TORC1.
Specimen part
View SamplesSalmonella enterica serotype Typhimurium cause a localized enteric infection in immunocompetent patients while human immunodeficiency virus (HIV)-infected patients develop a life threatening bacteremia. We used a rhesus macaque ileal loop model to study how simian immunodeficiency virus (SIV) infection triggers defects in mucosal barrier function that enhance S. Typhimurium dissemination. SIV infection resulted in significant depletion of CD4+ T cells in the intestinal mucosa. Gene expression profiling revealed a defective TH17 response (with suppression of IL-17 and IL-22 expression) and impaired homeostasis of the intestinal epithelium in SIV-infected animals during NTS infection. These findings correlated with an impaired ability of lamina propria CD4+ T cells from SIV-infected macaques to produce IL-17 upon ex vivo stimulation, while production of IFN-gamma was not affected. This cytokine imbalance in SIV-infected animals was associated with reduced expression of genes required for intestinal epithelial maintenance and repair, increased fluid secretion during NTS infection, epithelial damage and translocation of a non-invasive S. Typhimurium mutant. Although no defects in neutrophil recruitment were noted, the ileum of SIV-infected animals contained lower levels of the enzyme myeloperoxidase, which may indicate defects in neutrophil killing capacity. S. Typhimurium was recovered in markedly increased numbers from the mesenteric lymph nodes of SIV-infected macaques, illustrating the increased potential for systemic dissemination during co-infection. Our data suggest that SIV-infection causes a multi-factorial defect in mucosal barrier function that promotes bacterial dissemination.
Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis.
Specimen part, Disease, Cell line, Treatment
View SamplesThe goal of this study is to define a gene expression signature unique to DS-AMKL (acute megakaryoblastic leukemia or FAB M7 leukemia).
Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis.
Specimen part, Disease, Cell line
View SamplesIn this project, we studied a mouse model of human Down Syndrome (DS) megakaryocytic leukemia involving mutations in the GATA1 transcription factor (called GATA1s mutation). The model was generated through retroviral insertional mutagenesis in Gata1s mutant fetal liver progenitors. In this study, we analyzed the dependency of these leukemic cells on the Gata1s mutant protein.
Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis.
Specimen part, Cell line, Treatment
View SamplesThe goal of this study is to develop a Plag1 signature and determine how its overexpression contributes to leukemogenesis.
Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis.
Cell line
View SamplesThe goal of this study is to derive a mouse model of human Down Syndrome (DS) megakaryocytic leukemia involving mutations in the hematopoietic transcription factor, GATA1 (called GATA1s mutation). We achieved this through transduction of Gata1s mutant fetal progenitors by MSCV-based retrovirus expressing a GFP marker, followed by in vitro selection (for immortalized cell lines), and then in vivo selection (for transformed cell lines) through transplantation.
Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis.
Specimen part
View SamplesThe goal of this study is to derive a mouse model of human Down Syndrome (DS) megakaryocytic leukemia involving mutations in the hematopoietic transcription factor, GATA1 (called GATA1s mutation). We achieved this through transduction of Gata1s mutant fetal progenitors by MSCV-based retrovirus expressing a GFP marker, followed by in vitro selection (for immortalized cell lines), and then in vivo selection (for transformed cell lines) through transplantation.
Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis.
Specimen part
View SamplesThe goal of this study is to define the global gene expression profile of primary leukemic blasts from patients with different forms of myeloid leukemia and different FAB subtypes.
miR-125b-2 is a potential oncomiR on human chromosome 21 in megakaryoblastic leukemia.
Specimen part, Disease
View Samples