40 research outputs found

    DR haplotype diversity of the cynomolgus macaque as defined by its transcriptome

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    The DR region of particular primate species may display allelic polymorphism and gene copy number variation (region configuration polymorphism). The sum of these distinct types of polymorphism is defined as complexity. To date, however, the DR region of cynomolgus macaques (Macaca fascicularis) has been poorly defined. Transcriptome analysis of a pedigreed colony, comprising animals from Indonesia and Indochina, revealed a total of 15 Mafa-DRA and 57 DRB alleles, specifying 28 different region configurations. The DRA alleles can be divided into two distinct lineages. One lineage is polymorphic, but the majority of the amino acid replacements map to the leader peptide. The second lineage is at best oligomorphic, and segregates with one specific Mafa-DRB allele. The number of Mafa-DRB genes ranges from two to five per haplotype. Due to the presence of pseudogenes, however, each haplotype encodes only one to three bona fide DRB transcripts. Depending on the region configuration in which the Mafa-DRB gene is embedded, identical alleles may display differential transcription levels. Region configurations appear to have been generated by recombination-like events. When genes or gene segments are relocated, it seems plausible that they may be placed in the context of distinct transcription control elements. As such, DRB region-related transcription level differences may add an extra layer of polymorphism to this section of the adaptive immune system

    The Role of Sialyl Glycan Recognition in Host Tissue Tropism of the Avian Parasite Eimeria tenella

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    Eimeria spp. are a highly successful group of intracellular protozoan parasites that develop within intestinal epithelial cells of poultry, causing coccidiosis. As a result of resistance against anticoccidial drugs and the expense of manufacturing live vaccines, it is necessary to understand the relationship between Eimeria and its host more deeply, with a view to developing recombinant vaccines. Eimeria possesses a family of microneme lectins (MICs) that contain microneme adhesive repeat regions (MARR). We show that the major MARR protein from Eimeria tenella, EtMIC3, is deployed at the parasite-host interface during the early stages of invasion. EtMIC3 consists of seven tandem MAR1-type domains, which possess a high specificity for sialylated glycans as shown by cell-based assays and carbohydrate microarray analyses. The restricted tissue staining pattern observed for EtMIC3 in the chicken caecal epithelium indicates that EtMIC3 contributes to guiding the parasite to the site of invasion in the chicken gut. The microarray analyses also reveal a lack of recognition of glycan sequences terminating in the N-glycolyl form of sialic acid by EtMIC3. Thus the parasite is well adapted to the avian host which lacks N-glycolyl neuraminic acid. We provide new structural insight into the MAR1 family of domains and reveal the atomic resolution basis for the sialic acid-based carbohydrate recognition. Finally, a preliminary chicken immunization trial provides evidence that recombinant EtMIC3 protein and EtMIC3 DNA are effective vaccine candidates

    Transcriptomic Analysis of Toxoplasma Development Reveals Many Novel Functions and Structures Specific to Sporozoites and Oocysts

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    Sexual reproduction of Toxoplasma gondii occurs exclusively within enterocytes of the definitive felid host. The resulting immature oocysts are excreted into the environment during defecation, where in the days following, they undergo a complex developmental process. Within each oocyst, this culminates in the generation of two sporocysts, each containing 4 sporozoites. A single felid host is capable of shedding millions of oocysts, which can survive for years in the environment, are resistant to most methods of microbial inactivation during water-treatment and are capable of producing infection in warm-blooded hosts at doses as low as 1–10 ingested oocysts. Despite its extremely interesting developmental biology and crucial role in initiating an infection, almost nothing is known about the oocyst stage beyond morphological descriptions. Here, we present a complete transcriptomic analysis of the oocyst from beginning to end of its development. In addition, and to identify genes whose expression is unique to this developmental form, we compared the transcriptomes of developing oocysts with those of in vitro-derived tachyzoites and in vivo-derived bradyzoites. Our results reveal many genes whose expression is specifically up- or down-regulated in different developmental stages, including many genes that are likely critical to oocyst development, wall formation, resistance to environmental destruction and sporozoite infectivity. Of special note is the up-regulation of genes that appear “off” in tachyzoites and bradyzoites but that encode homologues of proteins known to serve key functions in those asexual stages, including a novel pairing of sporozoite-specific paralogues of AMA1 and RON2, two proteins that have recently been shown to form a crucial bridge during tachyzoite invasion of host cells. This work provides the first in-depth insight into the development and functioning of one of the most important but least studied stages in the Toxoplasma life cycle

    Toxoplasma gondii: identification of a developmentally regulated family of genes related to SAG2.

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    Previous studies have shown the surface of Toxoplasma gondii to be dominated by a family of proteins closely related to SAG1. In this study, we report the existence of a second family of genes defined by homology to SAG2. The predicted amino acid sequences of these three new proteins suggests that they are all glycosylphosphatidylinositol-linked surface antigens. All three also contain N-linked glycosylation sites, although their use has yet to be demonstrated. One of these SAG2-related antigens, SAG2B, is expressed in tachyzoites with an apparent size of 23 kDa. It is distinct, however, from the previously identified P23. In contrast to SAG2B, SAG2C and SAG2D appear to be expressed exclusively on the surface of bradyzoites. Analysis of the SAG2 family shows it to have weak but significant homology to the SAG1 family. Thus, all of the sequenced surface antigens of tachyzoites and many of those of bradyzoites fall into one large superfamily that can be divided into two subgroups defined by the prototypic and highly immunogenic SAG1 and SAG2, respectively

    Surface antigens of Toxoplasma gondii: variations on a theme.

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    Toxoplasma gondii is an obligate intracellular protozoan parasite with an exceptionally broad host range. Recently, it has become apparent that the number of surface antigens (SAGs) it expresses may rival the number of genera it can infect. Most of these antigens belong to the developmentally regulated and distantly related SAG1 or SAG2 families. The genes encoding the surface antigens are distributed throughout the T. gondii genome, with remarkably little polymorphism observed at each locus. Results from a number of studies have suggested that the surface antigens play an important role in the biology of the parasite. For example, SAG3 null mutants generated by targeted disruption provide convincing evidence that this surface antigen, at least, functions during parasite attachment. Analyses of a SAG1 knockout in rodents, however, indicate that this surface antigen may play a crucial role in immune modulation or virulence attenuation. The current understanding of the SAG1 and SAG2 families will be discussed here

    Surface antigens of Toxoplasma gondii: variations on a theme.

    No full text
    Toxoplasma gondii is an obligate intracellular protozoan parasite with an exceptionally broad host range. Recently, it has become apparent that the number of surface antigens (SAGs) it expresses may rival the number of genera it can infect. Most of these antigens belong to the developmentally regulated and distantly related SAG1 or SAG2 families. The genes encoding the surface antigens are distributed throughout the T. gondii genome, with remarkably little polymorphism observed at each locus. Results from a number of studies have suggested that the surface antigens play an important role in the biology of the parasite. For example, SAG3 null mutants generated by targeted disruption provide convincing evidence that this surface antigen, at least, functions during parasite attachment. Analyses of a SAG1 knockout in rodents, however, indicate that this surface antigen may play a crucial role in immune modulation or virulence attenuation. The current understanding of the SAG1 and SAG2 families will be discussed here
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