scholarly journals Transcriptional analysis shows a robust host response to Toxoplasma gondii during early and late chronic infection in both male and female mice

2019 ◽  
Author(s):  
Andrew L. Garfoot ◽  
Patrick W. Cervantes ◽  
Laura J. Knoll
Keyword(s):  
Toxoplasma Gondii ◽  
Chronic Infection ◽  
Host Response ◽  
Protozoan Parasite ◽  
Transcriptional Analysis ◽  
Dependent Manner ◽  
Male And Female ◽  
Female Mice ◽  
Chemokine Ligand ◽  
Host Genes

ABSTRACTThe long-term host effects caused by the protozoan parasite Toxoplasma gondii are poorly understood. RNA-seq analysis previously determined that the host response in the brain was higher and more complex at 28 versus 10 days postinfection. Here, we analyzed the host transcriptional profile of age-and sex-matched mice during early (21 and 28 days) and late (3 and 6 months) chronic infection. We found that a majority of the host genes which increase in abundance at day 21 postinfection are still increased 6 months postinfection for both male and female mice. While most of the differentially expressed genes were similar between sexes, females have far fewer genes that are significantly less abundant, which may lead to the slight increased cyst burden in males. Transcripts for C-X-C Motif Chemokine Ligand 13 (CXCL13) and a C-C Motif Chemokine Receptor 2 (CCR2) were significantly higher in females compared to males during infection. As T. gondii chronic infection and profilin (PRF) confer resistance to Listeria monocytogenes infection in a CCR2 dependent manner, the sex specific difference in CCR2 expression lead us to re-test the protection of PRF in both sexes. Chronic infection as well as PRF were nearly as effective at reducing the bacterial burden in male versus female mice. These data show that most of the differentially express host genes are similar between males and females, important differences exist leading us to emphasize the inclusion of both sexes for future studies.

scholarly journals Transcriptional Analysis Shows a Robust Host Response toToxoplasma gondiiduring Early and Late Chronic Infection in Both Male and Female Mice

2019 ◽  
Vol 87 (5) ◽  
Author(s):  
Andrew L. Garfoot ◽  
Patrick W. Cervantes ◽  
Laura J. Knoll
Keyword(s):  
Chronic Infection ◽  
Host Response ◽  
Differentially Expressed ◽  
Transcriptional Analysis ◽  
Sequencing Analysis ◽  
Dependent Manner ◽  
Male And Female ◽  
Content Type ◽  
Female Mice ◽  
Host Genes

ABSTRACTThe long-term host effects caused by the protozoan parasiteToxoplasma gondiiare poorly understood. High-throughput RNA sequencing analysis previously determined that the host response in the brain was greater and more complex at 28 days than at 10 days postinfection. Here, we analyzed the host transcriptional profile of age- and sex-matched mice during very early (21 days), early (28 days), mid (3 months), and late (6 months) chronic infection. We found that a majority of the host genes which increase in abundance at day 21 postinfection are still increased at 6 months postinfection for both male and female mice. While most of the differentially expressed genes were similar between sexes, females had far fewer genes that were significantly less abundant, which may have led to the slightly increased cyst burden in males. Transcripts for C-X-C motif chemokine ligand 13 and a C-C motif chemokine receptor 2 (CCR2) were significantly higher in females than in males during infection. AsT. gondiichronic infection and profilin (PRF) confer resistance toListeria monocytogenesinfection in a CCR2-dependent manner, the differences in CCR2 expression led us to retest the protection of PRF in both sexes. Male mice were nearly as effective as female mice at reducing the bacterial burden either with a chronic infection or when treated with PRF. These data show that most of the host genes differentially expressed in response toT. gondiiinfection are similar between males and females. While differences in transcript abundance exist between the sexes, the infection phenotypes tested here did not show significant differences.

scholarly journals Genetic approaches to studying virulence and pathogenesis in Toxoplasma gondii

2002 ◽  
Vol 357 (1417) ◽  
pp. 81-88 ◽  
Author(s):  
L. David Sibley ◽  
Dana G. Mordue ◽  
Chunlei Su ◽  
Paul M. Robben ◽  
Dan K. Howe
Keyword(s):  
Toxoplasma Gondii ◽  
Linkage Mapping ◽  
Protozoan Parasite ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genetic Studies ◽  
Microarray Studies ◽  
Expressed Sequence ◽  
Surprising Finding ◽  
Host Genes

Toxoplasma gondii is a common protozoan parasite that causes disease in immunocompromised humans. Equipped with a wide array of experimental tools, T. gondii has rapidly developed as a model parasite for genetic studies. The population structure of T. gondii is highly clonal, consisting of three distinct lineages that differ dramatically in virulence. Acute virulence is probably mediated by the genetic differences that distinguish strain types. We have utilized a combination of genetic approaches to investigate the acute virulence of toxoplasmosis using the mouse model. These studies reveal the surprising finding that pathogenicity is due to the over–stimulation of normally protective immune responses. Classical genetic linkage mapping studies indicate that genes that mediate acute virulence are linked to chromosome VII in the parasite. To increase the resolution of genetic mapping studies, single–nucleotide polymorphisms are being developed based on an extensive database of expressed sequence tags (ESTs) from T. gondii . Separately, DNA microarray studies are being used to examine the expression of parasite and host genes during infection. Collectively, these approaches should improve current understanding of virulence and pathogenicity in toxoplasmosis.

scholarly journals Prolonged low-dose dioxin exposure impairs metabolic adaptability to high-fat diet feeding in female but not male mice

2020 ◽  
Author(s):  
Geronimo Matteo ◽  
Myriam P Hoyeck ◽  
Hannah L Blair ◽  
Julia Zebarth ◽  
Kayleigh RC Rick ◽  
...  
Keyword(s):  
Glucose Homeostasis ◽  
High Fat Diet ◽  
Plasma Insulin ◽  
Low Dose ◽  
Dependent Manner ◽  
High Fat ◽  
Male And Female ◽  
Female Mice ◽  
Insulin Levels ◽  
Plasma Insulin Levels

AbstractObjectiveHuman studies consistently show an association between exposure to persistent organic pollutants, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, aka “dioxin”), and increased diabetes risk. We previously showed that acute high-dose TCDD exposure (20 μg/kg) decreased plasma insulin levels in both male and female mice in vivo; however, effects on glucose homeostasis were sex-dependent. The purpose of this study was to determine whether prolonged exposure to a physiologically relevant dose of TCDD impairs beta cell function and/or glucose homeostasis in a sex-dependent manner in either chow-fed or HFD-fed mice.MethodsMale and female mice were exposed to 20 ng/kg/d TCDD 2x/week for 12 weeks, and simultaneously fed a chow or 45% high-fat diet (HFD). Glucose metabolism was assessed by glucose and insulin tolerance tests throughout the study. Islets were isolated from females at 12 weeks for Tempo-Seq® analysis.ResultsLow-dose TCDD exposure did not lead to adverse metabolic consequences in chow-fed male or female mice, or in HFD-fed males. However, TCDD accelerated the onset of HFD-induced hyperglycemia and impaired glucose-induced plasma insulin levels in female mice. In addition, islet TempO-Seq® analysis showed that TCDD exposure promoted abnormal changes to endocrine and metabolic pathways in HFD-fed females.ConclusionsOur data suggest that TCDD exposure is more deleterious when combined with HFD-feeding in female mice, and that low-dose TCDD exposure increases diabetes susceptibility in females.

Bitter Taste Receptors, T2R138 and T2R16, are Induced in the Large Intestine of Male and Female Mice on a High Fat Diet in a Microbiota-Dependent Manner

2017 ◽  
Vol 152 (5) ◽  
pp. S156
Author(s):  
Filippo Caremoli ◽  
Jennifer Huynh ◽  
Venu Lagishetty ◽  
Jonathan Jacobs ◽  
Jonathan Braun ◽  
...  
Keyword(s):  
Large Intestine ◽  
High Fat Diet ◽  
Bitter Taste ◽  
Taste Receptors ◽  
Dependent Manner ◽  
High Fat ◽  
Male And Female ◽  
Female Mice ◽  
Bitter Taste Receptors

scholarly journals A Pseudouridine Synthase Homologue Is Critical to Cellular Differentiation in Toxoplasma gondii

2009 ◽  
Vol 8 (3) ◽  
pp. 398-409 ◽  
Author(s):  
Matthew Z. Anderson ◽  
Jeremy Brewer ◽  
Upinder Singh ◽  
John C. Boothroyd
Keyword(s):  
Toxoplasma Gondii ◽  
Chronic Infection ◽  
Insertional Mutagenesis ◽  
Protozoan Parasite ◽  
The United States ◽  
Rna Modification ◽  
Wild Type ◽  
Coding Region ◽  
Pseudouridine Synthase

ABSTRACT Toxoplasma gondii is a haploid protozoan parasite infecting about one in seven people in the United States. Key to the worldwide prevalence of T. gondii is its ability to establish a lifelong, chronic infection by evading the immune system, and central to this is the developmental switch between the two asexual forms, tachyzoites and bradyzoites. A library of mutants defective in tachyzoite-to-bradyzoite differentiation (Tbd−) was created through insertional mutagenesis. This library contains mutants that, compared to the wild type, are between 20% and 74% as efficient at stage conversion. Two mutants, TBD5 and TBD8, with disruptions in a gene encoding a putative pseudouridine synthase, PUS1, were identified. The disruption in TBD8 is in the 5′ end of the PUS1 gene and appears to produce a null allele with a 50% defect in differentiation. This is about the same switch efficiency as obtained with an engineered pus1 deletion mutant (Δpus1). The insertion in TBD5 is within the PUS1 coding region, and this appears to result in a more extreme phenotype of only ∼10% switch efficiency. Complementation of TBD8 with the genomic PUS1 allele restored wild-type differentiation efficiency. Infection of mice with pus1 mutant strains results in increased mortality during the acute phase and higher cyst burdens during the chronic infection, demonstrating an aberrant differentiation phenotype in vivo due to PUS1 disruption. Our results suggest a surprising and important role for RNA modification in this biological process.

Abstract 220: Transcriptional Analysis Of Caveolin And Cavin In The Male And Female Ageing Mouse Heart Following Ischemic Stress

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Can J Kiessling ◽  
Melissa Reichelt ◽  
John Headrick ◽  
Kevin Ashton
Keyword(s):  
G Protein ◽  
Ischemic Tolerance ◽  
Transcriptional Analysis ◽  
Membrane Microdomains ◽  
G Protein Coupled Receptor ◽  
Male And Female ◽  
Female Mice ◽  
Age Related ◽  
G Protein Coupled ◽  
Ischemic Stress

Cardioprotection against infarction and dysfunction in the myocardium involves G-protein-coupled receptor signalling orchestrated by specialised membrane microdomains termed caveolae. The caveolin protein family consist of three subtypes: caveolin-1, −2 and −3 (Cav1-3) and are responsible for the formation of caveolae and hypothesized to orchestrate cardioprotective signalling. Caveolin-3 deficiency and overexpression has been shown to attenuate and restore cardioprotection, respectively. Recently, a family of four related proteins known as cavins (Cavin1-4) have been implicated as regulators of caveolae formation and function. The roles and expression distribution of the cavin family is currently unknown in cardiac tissue. In this study hearts were isolated from 8, 16, 32 and 48 week male and female mice and subjected to normoxic perfusion (80 min) or ischemic stress (20 min global ischemia, 60 min reperfusion). RT-qPCR was used to assess differential gene expression of caveolin and cavin subtypes across these ages in both sexes. Decreased post-ischemic pressure development and increased LDH release were observed in 32 and 48 week old relative to 8 week old male hearts hearts, indicative of age-related loss of ischemic tolerance. Females showed greater tolerance to ischemia at 32 and 48 week old hearts when compared to male counterparts. In normoxic male 48 week old hearts, Cav1,-2,-3 and Cavin1 were significantly repressed, whilst post-ischemic male 48 week old hearts demonstrated significant repression of Cav3 and Cavin1 only. Normoxic female hearts showed no significant changes in caveolin and cavin transcript expression over the aging time course. However, post-ischemic female 48 week old hearts showing significant down-regulation of Cav3 only. Taken together, alterations in caveolin and cavin expression may contribute to the age-related loss of ischemic tolerance and G-protein-coupled receptor-mediated protection in aging male and female mice hearts.

scholarly journals Chronic infection of Toxoplasma gondii downregulates miR-132 expression in multiple brain regions in a sex-dependent manner

Parasitology ◽  
2014 ◽  
Vol 142 (04) ◽  
pp. 623-632 ◽  
Author(s):  
YE LI ◽  
GEETHA KANNAN ◽  
MIKHAIL V. PLETNIKOV ◽  
ROBERT H. YOLKEN ◽  
JIANCHUN XIAO
Keyword(s):  
Toxoplasma Gondii ◽  
Chronic Infection ◽  
Brain Regions ◽  
Dependent Manner

scholarly journals Sexual Dimorphism in Doxorubicin-induced Systemic Inflammation: Implications for Hepatic Cytochrome P450 Regulation

2020 ◽  
Vol 21 (4) ◽  
pp. 1279
Author(s):  
Marianne K.O. Grant ◽  
Ibrahim Y. Abdelgawad ◽  
Christine A. Lewis ◽  
Beshay N. Zordoky
Keyword(s):  
Sex Differences ◽  
Cytochrome P450 ◽  
Sexual Dimorphism ◽  
Inflammatory Response ◽  
Systemic Inflammation ◽  
Dependent Manner ◽  
Male And Female ◽  
Female Mice ◽  
Organ Toxicity ◽  
Hepatic Cytochrome

Doxorubicin (DOX) is an effective chemotherapeutic agent used to treat a wide variety of malignancies. In addition to its multi-organ toxicity, DOX treatment has been shown to induce systemic inflammation in patients and experimental animals. Inflammation alters the expression of hepatic cytochrome P450 (CYP) enzymes, which play important roles in drug metabolism and DOX-induced toxicity. Significant sex differences have been reported in DOX-induced toxicity; however, sex differences in DOX-induced systemic inflammation and the potential effects on hepatic CYP expression have not been determined. In the current work, male and female C57Bl/6 mice were administered DOX (20 mg/kg by intraperitoneal injection), and groups of mice were sacrificed 24 and 72 h after DOX administration. DOX elicited a systemic inflammatory response in both male and female mice, but the inflammatory response was stronger in male mice. DOX altered the expression of hepatic CYP isoforms in a sex-dependent manner. Most notably, inhibition of Cyp2c29 and Cyp2e1 was stronger in male than in female mice, which paralleled the sex differences in systemic inflammation. Therefore, sex differences in DOX-induced systemic inflammation may lead to sexually dimorphic drug interactions, in addition to contributing to the previously reported sexual dimorphism in specific DOX-induced organ toxicity.

scholarly journals Brain Toxicokinetics of Prometryne in Mice

2010 ◽  
Vol 61 (1) ◽  
pp. 19-27 ◽  
Author(s):  
Domagoj Đikić ◽  
Lana Sajli ◽  
Vesna Benković ◽  
Anica Knežević ◽  
Gordana Brozović ◽  
...  
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Time Dependent ◽  
Food Plants ◽  
Dependent Manner ◽  
Male Mice ◽  
Triazine Herbicide ◽  
Male And Female ◽  
Female Mice ◽  
Herbicide Atrazine

Brain Toxicokinetics of Prometryne in MicePrometryne is a methylthio-s-triazine herbicide. Significant trace amounts are found in the environment, mainly in water, soil, and food plants. The aim of this study was to establish brain and blood prometryne levels after single oral dose (1 g kg-1) in adult male and female mice. Prometryne was measured using the GC/MS assay at 1, 2, 4, 8, and 24 h after prometryne administration. Peak brain and blood prometryne values were observed 1 h after administration and they decreased in a time-dependent manner. Male mice had consistently higher brain and blood prometryne levels than female mice. The observed prometryne kinetics was similar to that reported for the structurally related herbicide atrazine.

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