The liver stages of malaria sporozoites develop in the hepatocyte cytoplasm inside a parasitophorous vacuole (PV). The circumsporozoite (CS) protein, the major surface protein of sporozoites, traverses the PV membrane and enters the cytoplasm and nucleus of hepatocytes. CS export into the cytoplasm requires the presence of pexel/VTS motifs. The transport of CS into the host nucleus is then mediated by importin (Imp) alpha3/beta1 that binds to the nuclear localization signal of CS localized in the conserved region II-plus. The NLSs of CS and of NFkB p50 share the same Imp. The entry of NFkB p50 into the nucleus is strongly inhibited in cell lines expressing CS, and in infected hepatocytes. Micro-array data from CS expressing cell line shows that 40 NFkB targets were significantly down regulated. Among them inflammation related MIP3a and PTGS transcripts were 65 and 22 fold down regulated, thus explaining the notable absence of inflammatory cells surrounding exo-erythrocytic forms (EEFs). The presence of CS in the cytoplasm of hepatocytes enhances EEF growth both in vitro and in vivo. Therefore Plasmodium blood stages and EEFs use the same strategy to secrete proteins into the cytoplasm of host cells and remodel it to the parasites advantage.
Plasmodium circumsporozoite protein promotes the development of the liver stages of the parasite.
No sample metadata fields
View SamplesCorticosteroids have been prescribed for decades to modulate inflammation, yet there is a paucity of data on their effects in humans. We examined the changes in cellular and molecular immune system parameters, or immunome, in 20 volunteers at baseline, and after intravenous hydrocortisone (HC) administered at moderate (250 mg) and low (50 mg) doses, to provide insight into how corticosteroids exert their effects.
Effects of Systemically Administered Hydrocortisone on the Human Immunome.
Sex, Age, Specimen part, Race, Subject, Time
View SamplesHuman peripheral monocytes have been categorized into three subsets based on differential expression levels of CD14 and CD16. However, the factors that influence the distribution of monocyte subsets and the roles which each subset plays in autoimmunity are not well studied. To compare the gene expression profiling 1) on intermediate monocytes CD14++CD16+ monocytes between healthy donors and autoimmune uveitis patients and 2) among 3 monocyte subsets in health donors, here we purified circulating intermediate CD14++CD16+ monocytes from 5 patients with autoimmune uveitis (labeled as P1-5) and 4 healthy donors (labeled as HD1-4) by flow cytometry and isolated total RNA to proceed microarray assay. In addition, we also purified CD14+CD16++ (non-classical monocytes) and CD14++CD16- (classical monocytes) from 4 healthy donors to do microarray. We demonstrate that CD14++CD16+ monocytes from patients and healthy control donors share a similar gene expression profile. The CD14+CD16++ cells (non-classical monocytes) display the most distinctive gene expression profiling when compared to intermediate CD14++CD16+ monocytes and classical CD14++CD16- monocytes.
CD14++CD16+ Monocytes Are Enriched by Glucocorticoid Treatment and Are Functionally Attenuated in Driving Effector T Cell Responses.
Specimen part, Disease stage, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of human germinal center light and dark zone cells and their relationship to human B-cell lymphomas.
Specimen part
View SamplesMicroarrays of gene expression in human germinal center light zone and dark zone B cells sorted according to the expression of cell surface molecules CD83 and CXCR4
Identification of human germinal center light and dark zone cells and their relationship to human B-cell lymphomas.
Specimen part
View SamplesMicroarrays of gene expression in mouse germinal center light zone and dark zone B cells sorted according to the expression of cell surface molecules CD83 and CXCR4
Identification of human germinal center light and dark zone cells and their relationship to human B-cell lymphomas.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Hypomethylation of the IL17RC promoter associates with age-related macular degeneration.
Age, Specimen part, Disease, Cell line
View SamplesAge related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly population worldwide. While recent studies have demonstrated strong genetic associations of single nucleotide polymorphisms within a number of genes and AMD, other modes of regulation are also likely to play a role in its aetiology. We undertook DNA methylation microarray analysis on monozygotic and dizygotic twins who were discordant for AMD and identified methylated IL17RC promoters as being present only in non-AMD control individuals rather than in AMD patients. We validated this finding of a significantly decreased level of methylation on the IL17RC promoter in AMD siblings as well as in a case control study involving 202 genetically unrelated AMD patients and 96 controls (95% CI, 0.03-0.17, P=3.1x10-8). Further, we showed that hypomethylation of the IL17RC promoter in AMD patients led to an elevated expression of its protein and mRNA in peripheral blood as well as in the retina and choroid, suggesting that the DNA methylation pattern and expression of IL17RC may potentially serve as a biomarker for the diagnosis of AMD and likely plays a role in disease pathogenesis.
Hypomethylation of the IL17RC promoter associates with age-related macular degeneration.
Specimen part, Cell line
View SamplesBackground
Hypomethylation of the IL17RC promoter associates with age-related macular degeneration.
Age, Specimen part
View SamplesSomatic hypermutation (SHM) and class switch recombination (CSR) increase the affinity and diversify the effector functions of antibodies during immune responses. Although SHM and CSR are fundamentally different, their independent roles in regulating B cell fate have been difficult to uncouple because a single enzyme, activation-induced cytidine deaminase (encoded by Aicda), initiates both reactions. Here, we used a combination of Aicda and antibody mutant alleles that separate the effects of CSR and SHM on polyclonal immune responses. We found that class-switching to IgG1 biased the fate choice made by B cells, favoring the plasma cell over memory cell fate without significantly affecting clonal expansion in the germinal center (GC). In contrast, SHM reduced the longevity of memory B cells by creating polyreactive specificities that were selected against over time. Our data define the independent contributions of SHM and CSR to the generation and persistence of memory in the antibody system. Overall design: IgG1 and IgM light zone (LZ) and dark zone (DZ) germinal center (GC) B cells were compared in immunized AIDcre/- IgH-96K/+ R26-LSL-YFP mice.
Independent Roles of Switching and Hypermutation in the Development and Persistence of B Lymphocyte Memory.
Specimen part, Cell line, Subject
View Samples