Project description:Entamoeba histolytica is a protozoan parasite that causes colitis and liver abscesses. Several Entamoeba species and strains with differing levels of virulence have been identified. E. histolytica HM-1:IMSS is a virulent strain, E. histolytica Rahman is a nonvirulent strain, and Entamoeba dispar is a nonvirulent species. We used an E. histolytica DNA microarray consisting of 2,110 genes to assess the transcriptional differences between these species/strains with the goal of identifying genes whose expression correlated with a virulence phenotype. We found 415 genes expressed at lower levels in E. dispar and 32 genes with lower expression in E. histolytica Rahman than in E. histolytica HM-1:IMSS. Overall, 29 genes had decreased expression in both the nonvirulent species/strains than the virulent E. histolytica HM-1:IMSS. Interestingly, a number of genes with potential roles in stress response and virulence had decreased expression in either one or both nonvirulent Entamoeba species/strains. These included genes encoding Fe hydrogenase (9.m00419), peroxiredoxin (176.m00112), type A flavoprotein (6.m00467), lysozyme (6.m00454), sphingomyelinase C (29.m00231), and a hypothetical protein with homology to both a Plasmodium sporozoite threonine-asparagine-rich protein (STARP) and a streptococcal hemagglutinin (238.m00054). The function of these genes in Entamoeba and their specific roles in parasite virulence need to be determined. We also found that a number of the non-long-terminal-repeat retrotransposons (EhLINEs and EhSINEs), which have been shown to modulate gene expression and genomic evolution, had lower expression in the nonvirulent species/strains than in E. histolytica HM-1:IMSS. Our results, identifying expression profiles and patterns indicative of a virulence phenotype, may be useful in characterizing the transcriptional framework of virulence. A species experiment design type assays differences between distinct species. Keywords: species_design

Project description:Resistance to amebiasis is associated with a polymorphism in the leptin receptor. Previous studies demonstrated that humans with the ancestral Q223 leptin receptor allele were nearly four times less likely to be infected with Entamoeba histolytica than those carrying the mutant R223 allele. We hypothesized that the Q223 allele protected against E. histolytica via STAT3-mediated transcription of genes required for mucosal immunity. To test this, mice containing the humanized LEPR Q or R allele at codon 223 were intracecally infected with E. histolytica. Susceptibility to amebiasis was assessed, and cecal tissues analyzed for changes in gene expression. By 72 h post-challenge all Q223 mice had cleared E. histolytica, whereas 39% of 223R mice were infected. 37 genes were differentially expressed in response to infection at 72 h, including pro-inflammatory genes (CXCL2, calprotectin (S100A8/9), Pla2g7, Itbg2, and MMP9) and functions pertaining to the movement and activity of immune cells. A comparison at 12 h post-challenge of infected Q223 vs. R223 mice identified a subset of differentially-expressed genes, many of which were closely linked to leptin signaling. Further analyses indicated that the Q223 gene expression pattern was consistent with a suppressed apoptotic response to infection, while 223R showed increased cellular proliferation and recruitment. These studies are the first to illuminate the downstream effects of leptin receptor polymorphisms on intestinal infection by E. histolytica. As such, they are important for the insight that they provide to this previously uncharacterized mechanism of mucosal immunity. Resistance to amebiasis is associated with a polymorphism in the leptin receptor. Previous studies demonstrated that humans with the ancestral Q223 leptin receptor allele were nearly four times less likely to be infected with Entamoeba histolytica than those carrying the mutant R223 allele. We hypothesized that the Q223 allele protected against E. histolytica via STAT3-mediated transcription of genes required for mucosal immunity. To test this, mice containing the humanized LEPR Q or R allele at codon 223 were intracecally infected with E. histolytica. Susceptibility to amebiasis was assessed, and cecal tissues analyzed for changes in gene expression. By 72 h post-challenge all Q223 mice had cleared E. histolytica, whereas 39% of 223R mice were infected. 37 genes were differentially expressed in response to infection at 72 h, including pro-inflammatory genes (CXCL2, calprotectin (S100A8/9), Pla2g7, Itbg2, and MMP9) and functions pertaining to the movement and activity of immune cells. A comparison at 12 h post-challenge of infected Q223 vs. R223 mice identified a subset of differentially-expressed genes, many of which were closely linked to leptin signaling. Further analyses indicated that the Q223 gene expression pattern was consistent with a suppressed apoptotic response to infection, while 223R showed increased cellular proliferation and recruitment. These studies are the first to illuminate the downstream effects of leptin receptor polymorphisms on intestinal infection by E. histolytica. As such, they are important for the insight that they provide to this previously uncharacterized mechanism of mucosal immunity.

Project description:Resistance to amebiasis is associated with a polymorphism in the leptin receptor. Previous studies demonstrated that humans with the ancestral Q223 leptin receptor allele were nearly four times less likely to be infected with Entamoeba histolytica than those carrying the mutant R223 allele. We hypothesized that the Q223 allele protected against E. histolytica via STAT3-mediated transcription of genes required for mucosal immunity. To test this, mice containing the humanized LEPR Q or R allele at codon 223 were intracecally infected with E. histolytica. Susceptibility to amebiasis was assessed, and cecal tissues analyzed for changes in gene expression. By 72 h post-challenge all Q223 mice had cleared E. histolytica, whereas 39% of 223R mice were infected. 37 genes were differentially expressed in response to infection at 72 h, including pro-inflammatory genes (CXCL2, calprotectin (S100A8/9), Pla2g7, Itbg2, and MMP9) and functions pertaining to the movement and activity of immune cells. A comparison at 12 h post-challenge of infected Q223 vs. R223 mice identified a subset of differentially-expressed genes, many of which were closely linked to leptin signaling. Further analyses indicated that the Q223 gene expression pattern was consistent with a suppressed apoptotic response to infection, while 223R showed increased cellular proliferation and recruitment. These studies are the first to illuminate the downstream effects of leptin receptor polymorphisms on intestinal infection by E. histolytica. As such, they are important for the insight that they provide to this previously uncharacterized mechanism of mucosal immunity. Resistance to amebiasis is associated with a polymorphism in the leptin receptor. Previous studies demonstrated that humans with the ancestral Q223 leptin receptor allele were nearly four times less likely to be infected with Entamoeba histolytica than those carrying the mutant R223 allele. We hypothesized that the Q223 allele protected against E. histolytica via STAT3-mediated transcription of genes required for mucosal immunity. To test this, mice containing the humanized LEPR Q or R allele at codon 223 were intracecally infected with E. histolytica. Susceptibility to amebiasis was assessed, and cecal tissues analyzed for changes in gene expression. By 72 h post-challenge all Q223 mice had cleared E. histolytica, whereas 39% of 223R mice were infected. 37 genes were differentially expressed in response to infection at 72 h, including pro-inflammatory genes (CXCL2, calprotectin (S100A8/9), Pla2g7, Itbg2, and MMP9) and functions pertaining to the movement and activity of immune cells. A comparison at 12 h post-challenge of infected Q223 vs. R223 mice identified a subset of differentially-expressed genes, many of which were closely linked to leptin signaling. Further analyses indicated that the Q223 gene expression pattern was consistent with a suppressed apoptotic response to infection, while 223R showed increased cellular proliferation and recruitment. These studies are the first to illuminate the downstream effects of leptin receptor polymorphisms on intestinal infection by E. histolytica. As such, they are important for the insight that they provide to this previously uncharacterized mechanism of mucosal immunity. Control (non-infected QQ or RR) vs. infected with E. histolytica at two time points (12hour and 72 hour)

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Transcriptional profiling of Entamoeba histolytica trophozoites

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