scholarly journals Dynamics of Gene Expression in Mice Infected with Different Genotypes of Toxoplasma gondii

2019 ◽  
Author(s):  
Li Yu ◽  
Keats Shwab ◽  
Rachel D Hill ◽  
Xing-Quan zhu ◽  
Julia S Gouffon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Toxoplasma Gondii ◽  
Early Phase ◽  
Late Phase ◽  
Type I ◽  
Type Ii ◽  
Type Iii ◽  
Peak Expression ◽  
Virulent Type

Abstract Background: Toxoplasma gondii is genetically diverse and different genotypes differ markedly in phenotype. The present study aims to define transcriptional patterns and biological processes that characterize host response to distinct strains of T. gondii. Methods: We conducted a time course study of gene expression microarray in mice during acute infection (days 1 to 7) with the highly virulent type I (GT1 strain), intermediately virulent type II (PTG strain) and non-virulent type III (CTG strain) parasites. Results: Overall, the number of genes affected increased from day 1 to day 5, and decreased on day 7. However, type III and type II infections up-regulated more genes than did type I at the very early phase, whereas type I infection up-regulated more genes at the late phase. Gene ontology (GO) analysis showed that the genes related to inflammatory and immune response were mostly affected and the majority were up-regulated, with type III infection inducing a higher degree of change and affecting more genes than did type I at the early phase. However, this pattern was reversed at the late phase. The change of expression during type II infection was between that of types I and III. Many genes associated with inflammatory and immune responses showed bimodal effects, with the first peak expression mostly at day 3 and then a second peak expression mostly at day 5. Several differentially expressed genes, including INF-γ, iNOS, CXCL10/IP-10, and numerous immunity-related GTPases (IRGs) and guanylate-binding proteins (GBPs) were previously experimentally confirmed important host factors in controlling T. gondii infection. Bioinformatic analysis of biological pathways enriched during infection revealed upregulation of pathways relating to cell-mediated immunity and the inflammatory response during all three infection types, though such enrichment was most expansive and pronounced during type I infection, and much less pronounced during type III infection. Conclusions: The findings in our study revealed dynamic differences of gene expression and different pathways of immune response in mice infected with three distinct strains of T. gondii.

scholarly journals Transepithelial Migration of Toxoplasma gondii Is Linked to Parasite Motility and Virulence

2002 ◽  
Vol 195 (12) ◽  
pp. 1625-1633 ◽  
Author(s):  
Antonio Barragan ◽  
L. David Sibley
Keyword(s):  
Toxoplasma Gondii ◽  
Ex Vivo ◽  
Type I ◽  
Type Ii ◽  
Long Distance ◽  
Type Iii ◽  
Migratory Capacity ◽  
Virulent Type ◽  
Parasite Motility

After oral ingestion, Toxoplasma gondii crosses the intestinal epithelium, disseminates into the deep tissues, and traverses biological barriers such as the placenta and the blood-brain barrier to reach sites where it causes severe pathology. To examine the cellular basis of these processes, migration of T. gondii was studied in vitro using polarized host cell monolayers and extracellular matrix. Transmigration required active parasite motility and the highly virulent type I strains consistently exhibited a superior migratory capacity than the nonvirulent type II and type III strains. Type I strain parasites also demonstrated a greater capacity for transmigration across mouse intestine ex vivo, and directly penetrated into the lamina propria and vascular endothelium. A subpopulation of virulent type I parasites exhibited a long distance migration (LDM) phenotype in vitro, that was not expressed by nonvirulent type II and type III strains. Cloning of parasites expressing the LDM phenotype resulted in substantial increase of migratory capacity in vitro and in vivo. The potential to up-regulate migratory capacity in T. gondii likely plays an important role in establishing new infections and in dissemination upon reactivation of chronic infections.

scholarly journals Differential Effects of Three CanonicalToxoplasmaStrains on Gene Expression in Human Neuroepithelial Cells

2010 ◽  
Vol 79 (3) ◽  
pp. 1363-1373 ◽  
Author(s):  
Jianchun Xiao ◽  
Lorraine Jones-Brando ◽  
C. Conover Talbot ◽  
Robert H. Yolken
Keyword(s):  
Gene Expression ◽  
Central Nervous System ◽  
Nervous System ◽  
Nucleotide Metabolism ◽  
Neural Cells ◽  
Type I ◽  
Type Ii ◽  
Type Iii ◽  
Neuroepithelial Cells ◽  
The Central Nervous System

ABSTRACTStrain type is one of the key factors suspected to play a role in determining the outcome ofToxoplasmainfection. In this study, we examined the transcriptional profile of human neuroepithelioma cells in response to representative strains ofToxoplasmaby using microarray analysis to characterize the strain-specific host cell response. The study of neural cells is of interest in light of the ability ofToxoplasmato infect the brain and to establish persistent infection within the central nervous system. We found that the extents of the expression changes varied considerably among the three strains. Neuroepithelial cells infected withToxoplasmatype I exhibited the highest level of differential gene expression, whereas type II-infected cells had a substantially smaller number of genes which were differentially expressed. Cells infected with type III exhibited intermediate effects on gene expression. The three strains also differed in the individual genes and gene pathways which were altered following cellular infection. For example, gene ontology (GO) analysis indicated that type I infection largely affects genes related to the central nervous system, while type III infection largely alters genes which affect nucleotide metabolism; type II infection does not alter the expression of a clearly defined set of genes. Moreover, Ingenuity Pathways Analysis (IPA) suggests that the three lineages differ in the ability to manipulate their host; e.g., they employ different strategies to avoid, deflect, or subvert host defense mechanisms. These observed differences may explain some of the variation in the neurobiological effects of different strains ofToxoplasmaon infected individuals.

scholarly journals Ovarian Steroids Differentially Modulate the Gene Expression of Gonadotropin-Releasing Hormone Neuronal Subtypes in the Ovariectomized Cynomolgus Monkey

2003 ◽  
Vol 88 (2) ◽  
pp. 655-662 ◽  
Author(s):  
Sally J. Krajewski ◽  
Ty W. Abel ◽  
Mary Lou Voytko ◽  
Naomi E. Rance
Keyword(s):  
Gene Expression ◽  
Cynomolgus Monkey ◽  
Hormone Treatment ◽  
Nucleus Basalis ◽  
Nucleus Basalis Of Meynert ◽  
Type I ◽  
Type Ii ◽  
Type Iii ◽  
Gnrh Neurons ◽  
Gene Transcripts

In the present study, we compared the morphology and distribution of neurons expressing GnRH gene transcripts in the hypothalamus and forebrain of the cynomolgus monkey to that of the human. As in the human, three subtypes of GnRH neurons were identified. Type I GnRH neurons were small, oval cells with high levels of gene expression and were located within the basal hypothalamus. Type II GnRH neurons were small and sparsely labeled and were widely scattered in the hypothalamus, midline nuclei of the thalamus, and extended amygdala. Type III neurons displayed magnocellular morphology and intermediate labeling intensity and were located in the nucleus basalis of Meynert, caudate, and amygdala. In a second experiment, we determined the effect of estrogen or estrogen plus progesterone on the gene expression of GnRH neurons in the brains of young, ovariectomized cynomolgus monkeys. We report that hormone treatment resulted in a significant decrease in GnRH mRNA in type I neurons within the basal hypothalamus of ovariectomized monkeys. In contrast, there was no effect of hormone treatment on the gene expression of type III GnRH neurons in the nucleus basalis of Meynert. The present findings provide evidence that the increase in gene expression of type I GnRH neurons in postmenopausal women is secondary to the ovarian failure of menopause. The differential responses of type I and III GnRH neurons to hormone treatment provide additional evidence that distinct subpopulations of neurons expressing GnRH mRNA exist in the primate hypothalamus.

scholarly journals Type II Toxoplasma gondii Induction of CD40 on Infected Macrophages Enhances Interleukin-12 Responses

2014 ◽  
Vol 82 (10) ◽  
pp. 4047-4055 ◽  
Author(s):  
Pedro Morgado ◽  
Dattanand M. Sudarshana ◽  
Lanny Gov ◽  
Katherine S. Harker ◽  
Tonika Lam ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Transcript Level ◽  
Forward Genetics ◽  
Interleukin 12 ◽  
Type I ◽  
Dependent Manner ◽  
Type Ii ◽  
Content Type ◽  
Type Iii ◽  
Infected Cells

ABSTRACTToxoplasma gondiiis an obligate intracellular parasite that can cause severe neurological disease in infected humans. CD40 is a receptor on macrophages that plays a critical role in controllingT. gondiiinfection. We examined the regulation of CD40 on the surface ofT. gondii-infected bone marrow-derived macrophages (BMdMs).T. gondiiinduced CD40 expression both at the transcript level and on the cell surface, and interestingly, the effect was parasite strain specific: CD40 levels were dramatically increased in type IIT. gondii-infected BMdMs compared to type I- or type III-infected cells. Type II induction of CD40 was specific to cells harboring intracellular parasites and detectable as early as 6 h postinfection (hpi) at the transcript level. CD40 protein expression peaked at 18 hpi. Using forward genetics with progeny from a type II × type III cross, we found that CD40 induction mapped to a region of chromosome X that included the gene encoding the dense granule protein 15 (GRA15). Using type I parasites stably expressing the type II allele ofGRA15(GRA15II), we found that type I GRA15IIparasites induced the expression of CD40 on infected cells in an NF-κB-dependent manner. In addition, stable expression of hemagglutinin-tagged GRA15IIin THP-1 cells resulted in CD40 upregulation in the absence of infection. Since CD40 signaling contributes to interleukin-12 (IL-12) production, we examined IL-12 from infected macrophages and found that CD40L engagement of CD40 amplified the IL-12 response in type II-infected cells. These data indicate that GRA15IIinduction of CD40 promotes parasite immunity through the production of IL-12.

scholarly journals Differential Gene Expression in Mice Infected with Distinct Toxoplasma Strains

2011 ◽  
Vol 80 (3) ◽  
pp. 968-974 ◽  
Author(s):  
Rachel D. Hill ◽  
Julia S. Gouffon ◽  
Arnold M. Saxton ◽  
Chunlei Su
Keyword(s):  
Gene Expression ◽  
Parasite Burden ◽  
Type I ◽  
Type Ii ◽  
Gene Expression Response ◽  
Content Type ◽  
Type Iii ◽  
Clonal Type ◽  
Expression Response ◽  
Macrophage Populations

Toxoplasma gondiiis the causative agent of toxoplasmosis in human and animals. In a mouse model,T. gondiistrains can be divided into three groups, including the virulent, intermediately virulent, and nonvirulent. The clonal type I, II, and IIIT. gondiistrains belong to these three groups, respectively. To better understand the basis of virulence phenotypes, we investigated mouse gene expression responses to the infection of differentT. gondiistrains at day 5 after intraperitoneal inoculation with 500 tachyzoites. The transcriptomes of mouse peritoneal cells showed that 1,927, 1,573, and 1,009 transcripts were altered more than 2-fold by type I, II, and III infections, respectively, and that the majority of altered transcripts were shared. Overall transcription patterns were similar in type I and type II infections, and both had greater changes than infection with type III. Quantification of parasite burden in mouse spleens showed that the burden with type I infection was 1,000 times higher than that of type II and that the type II burden was 20 times higher than that of type III. Fluorescence-activated cell sorting revealed that type I and II infections had comparable macrophage populations, and both were higher than the population with type III infection. In addition, type I infection had a higher percentage of neutrophils than type II and III infections. Taken together, these results suggested that there is a common gene expression response toT. gondiiinfection in mice. This response is further modified by parasite strain-specific factors that determine their distinct virulence phenotypes.

scholarly journals The Toxoplasma gondii-Shuttling Function of Dendritic Cells Is Linked to the Parasite Genotype

2009 ◽  
Vol 77 (4) ◽  
pp. 1679-1688 ◽  
Author(s):  
Henrik Lambert ◽  
Polya P. Vutova ◽  
William C. Adams ◽  
Karin Loré ◽  
Antonio Barragan
Keyword(s):  
Dendritic Cells ◽  
Toxoplasma Gondii ◽  
Phenotypic Traits ◽  
Type I ◽  
Type Ii ◽  
Parasite Genotype ◽  
Type Iii ◽  
Parasite Motility

ABSTRACT Following intestinal invasion, the processes leading to systemic dissemination of the obligate intracellular protozoan Toxoplasma gondii remain poorly understood. Recently, tachyzoites representative of type I, II and III T. gondii populations were shown to differ with respect to their ability to transmigrate across cellular barriers. In this process of active parasite motility, type I strains exhibit a migratory capacity superior to those of the type II and type III strains. Data also suggest that tachyzoites rely on migrating dendritic cells (DC) as shuttling leukocytes to disseminate in tissue, e.g., the brain, where cysts develop. In this study, T. gondii tachyzoites sampled from the three populations were allowed to infect primary human blood DC, murine intestinal DC, or in vitro-derived DC and were compared for different phenotypic traits. All three archetypical lineages of T. gondii induced a hypermigratory phenotype in DC shortly after infection in vitro. Type II (and III) strains induced higher migratory frequency and intensity in DC than type I strains did. Additionally, adoptive transfer of infected DC favored the dissemination of type II and type III parasites over that of type I parasites in syngeneic mice. Type II parasites exhibited stronger intracellular association with both CD11c+ DC and other leukocytes in vivo than did type I parasites. Altogether, these findings suggest that infected DC contribute to parasite propagation in a strain type-specific manner and that the parasite genotype (type II) most frequently associated with toxoplasmosis in humans efficiently exploits DC migration for parasite dissemination.

scholarly journals Dissecting Amyloid Beta Deposition Using Distinct Strains of the Neurotropic Parasite Toxoplasma gondii as a Novel Tool

ASN NEURO ◽  
2017 ◽  
Vol 9 (4) ◽  
pp. 175909141772491 ◽  
Author(s):  
Carla M. Cabral ◽  
Kathryn E. McGovern ◽  
Wes R. MacDonald ◽  
Jenna Franco ◽  
Anita A. Koshy
Keyword(s):  
Toxoplasma Gondii ◽  
Amyloid Precursor Protein ◽  
Inflammatory Cytokines ◽  
Amyloid Beta ◽  
Parasite Burden ◽  
Precursor Protein ◽  
Mammalian Brain ◽  
Type I ◽  
Type Ii ◽  
Type Iii

Genetic and pathologic data suggest that amyloid beta (Aβ), produced by processing of the amyloid precursor protein, is a major initiator of Alzheimer’s disease (AD). To gain new insights into Aβ modulation, we sought to harness the power of the coevolution between the neurotropic parasite Toxoplasma gondii and the mammalian brain. Two prior studies attributed Toxoplasma-associated protection against Aβ to increases in anti-inflammatory cytokines (TGF-β and IL-10) and infiltrating phagocytic monocytes. These studies only used one Toxoplasma strain making it difficult to determine if the noted changes were associated with Aβ protection or simply infection. To address this limitation, we infected a third human amyloid precursor protein AD mouse model (J20) with each of the genetically distinct, canonical strains of Toxoplasma (Type I, Type II, or Type III). We then evaluated the central nervous system (CNS) for Aβ deposition, immune cell responses, global cytokine environment, and parasite burden. We found that only Type II infection was protective against Aβ deposition despite both Type II and Type III strains establishing a chronic CNS infection and inflammatory response. Compared with uninfected and Type I-infected mice, both Type II- and Type III-infected mice showed increased numbers of CNS T cells and microglia and elevated pro-inflammatory cytokines, but neither group showed a >2-fold elevation of TGF-β or IL-10. These data suggest that we can now use our identification of protective (Type II) and nonprotective (Type III) Toxoplasma strains to determine what parasite and host factors are linked to decreased Aβ burden rather than simply with infection.

scholarly journals Differential Regulation of Type I and Type III Interferon Signaling

2019 ◽  
Vol 20 (6) ◽  
pp. 1445 ◽  
Author(s):  
Megan L. Stanifer ◽  
Kalliopi Pervolaraki ◽  
Steeve Boulant
Keyword(s):  
Immune Response ◽  
Differential Regulation ◽  
Type I ◽  
Type Ii ◽  
Interferon Signaling ◽  
Type Iii ◽  
Type I Ifns ◽  
Current State ◽  
Type Iii Ifn ◽  
Type Iii Interferon

Interferons (IFNs) are very powerful cytokines, which play a key role in combatting pathogen infections by controlling inflammation and immune response by directly inducing anti-pathogen molecular countermeasures. There are three classes of IFNs: type I, type II and type III. While type II IFN is specific for immune cells, type I and III IFNs are expressed by both immune and tissue specific cells. Unlike type I IFNs, type III IFNs have a unique tropism where their signaling and functions are mostly restricted to epithelial cells. As such, this class of IFN has recently emerged as a key player in mucosal immunity. Since the discovery of type III IFNs, the last 15 years of research in the IFN field has focused on understanding whether the induction, the signaling and the function of these powerful cytokines are regulated differently compared to type I IFN-mediated immune response. This review will cover the current state of the knowledge of the similarities and differences in the signaling pathways emanating from type I and type III IFN stimulation.

scholarly journals IL-21 imposes a type II EBV gene expression on type III and type I B cells by the repression of C- and activation of LMP-1-promoter

2009 ◽  
Vol 107 (2) ◽  
pp. 872-877 ◽  
Author(s):  
L. L. Kis ◽  
D. Salamon ◽  
E. K. Persson ◽  
N. Nagy ◽  
F. A. Scheeren ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cells ◽  
Type I ◽  
Type Ii ◽  
Type Iii

Labelling of non-A, non-B hepatitis infected chimpanzee hepatocytes with nuclease-gold conjugates

1984 ◽  
Vol 42 ◽  
pp. 250-251
Author(s):  
G. D. Gagne ◽  
M. F. Miller ◽  
D. A. Peterson
Keyword(s):  
Endoplasmic Reticulum ◽  
Experimental Infection ◽  
Uranyl Acetate ◽  
Type I ◽  
Cellular Injury ◽  
Type Ii ◽  
Tubular Structures ◽  
Type Iii ◽  
Type Iv ◽  
Infected Chimpanzee

Experimental infection of chimpanzees with non-A, non-B hepatitis (NANB) or with delta agent hepatitis results in the appearance of characteristic cytoplasmic alterations in the hepatocytes. These alterations include spongelike inclusions (Type I), attached convoluted membranes (Type II), tubular structures (Type III), and microtubular aggregates (Type IV) (Fig. 1). Type I, II and III structures are, by association, believed to be derived from endoplasmic reticulum and may be morphogenetically related. Type IV structures are generally observed free in the cytoplasm but sometimes in the vicinity of type III structures. It is not known whether these structures are somehow involved in the replication and/or assembly of the putative NANB virus or whether they are simply nonspecific responses to cellular injury. When treated with uranyl acetate, type I, II and III structures stain intensely as if they might contain nucleic acids. If these structures do correspond to intermediates in the replication of a virus, one might expect them to contain DNA or RNA and the present study was undertaken to explore this possibility.

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