Parasite Manipulation of the Invariant Chain and the Peptide Editor H2-DM Affects Major Histocompatibility Complex Class II Antigen Presentation during Toxoplasma gondii Infection

Leroux, Louis‐Philippe; Nishi, Manami; El-Hage, Sandy; Fox, Barbara A.; Bzik, David J.; Dzierszinski, Florence

doi:10.1128/iai.00415-15

Cited by 15 publications

(19 citation statements)

References 82 publications

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“…Our observations are in agreement with others. Indeed, it has been shown the ability of T gondii infection to downregulate MHC II gene expression and antigen presentation on macrophages and DCs, though this has only previously been reported in vitro . Our results suggest a pregnancy‐related mechanism interfering with MHC II expression, and therefore, with antigen presentation during T gondii infection.…”

Section: Discussionmentioning

confidence: 49%

Toxoplasma gondii infection reduces serum progesterone levels and adverse effects at the maternal‐foetal interface

Brito

Silva

Castro

et al. 2019

Parasite Immunology

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Aims Pregnant BALB/c mice infected with a Toxoplasma gondii type II strain were used to determine how pregnancy interferes with the development of maternal immunity to T gondii and how infection disrupts pregnancy and foetal development. Methods Maternal and foetal parasite loads were assessed by amplification of T gondii SAG1 using qPCR. Adverse effects of infection were evaluated on foetal‐placental development by quantification of implantation units undergoing resorption and by histopathological analyses. Serum progesterone levels were quantified by immunoassay. The effect of T gondii infection on maternal immunity was determined by assessing the cellular composition of spleens by flow cytometry. Results Infected pregnant mice exhibited clinical signs of infection, inflammation and necrosis at the maternal‐foetal interface and decreased serum progesterone levels. In infected mice, there was a clear effect of pregnancy and infection on macrophage cell numbers. However, no differences in the parasite load were detected between non‐pregnant and pregnant mice. Conclusions Maternal T gondii infection induced adverse effects at the maternal‐foetal interface. Alterations were found in immune spleen cells, dependent on the day of pregnancy, relative to nonpregnant animals. The results obtained suggest a pregnancy‐dependent mechanism during T gondii infection able to interfere with macrophage numbers.

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Section: Discussionmentioning

confidence: 49%

Toxoplasma gondii infection reduces serum progesterone levels and adverse effects at the maternal‐foetal interface

Brito

Silva

Castro

et al. 2019

Parasite Immunology

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“…Bone marrow-derived macrophage differentiation. Bone marrow-derived macrophages (BMDM) were obtained by differentiating precursor cells from murine bone marrow (101). Briefly, mice were euthanized by CO 2 asphyxiation, hind legs were collected in Hanks' balanced salt solution (HBSS) (100 U/ml penicillin, 100 g/ml streptomycin, 4.2 mM sodium bicarbonate), and marrow was flushed out of bones.…”

Section: Methodsmentioning

confidence: 99%

“…Measurement of parasite replication by qPCR. Parasite replication in vitro was assessed by extracting genomic DNA (gDNA), followed by measuring the amplification of the T. gondii B1 gene by qPCR, as described previously (101). Briefly, BMDM cultures were plated in 12-well plates overnight; serum starved for 2 h in the presence of DMSO (vehicle), 20 nM rapamycin, or 200 nM Torin-1; and then inoculated with T. gondii tachyzoites (RH and ME49 strains) at an MOI of 1:20.…”

Section: Methodsmentioning

confidence: 99%

The Protozoan Parasite Toxoplasma gondii Selectively Reprograms the Host Cell Translatome

et al. 2018

Self Cite

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The intracellular parasite promotes infection by targeting multiple host cell processes; however, whether it modulates mRNA translation is currently unknown. Here, we show that infection of primary murine macrophages with type I or II strains causes a profound perturbation of the host cell translatome. Notably, translation of transcripts encoding proteins involved in metabolic activity and components of the translation machinery was activated upon infection. In contrast, the translational efficiency of mRNAs related to immune cell activation and cytoskeleton/cytoplasm organization was largely suppressed. Mechanistically, bolstered mechanistic target of rapamycin (mTOR) signaling to selectively activate the translation of mTOR-sensitive mRNAs, including those with a 5'-terminal oligopyrimidine (5' TOP) motif and those encoding mitochondrion-related proteins. Consistent with parasite modulation of host mTOR-sensitive translation to promote infection, inhibition of mTOR activity suppressed replication. Thus, selective reprogramming of host mRNA translation represents an important subversion strategy during infection.

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“…Recently, a pioneering study has investigated the metabolic needs and capabilities of T. gondii using a combined computational and experimental approach 10 . The interplay between T. gondii parasites and their hosts has been studied for decades using targeted approaches, such as the analysis of mutants or host immunological responses 11 12 . Although much has been learned from such studies, they focus on individual pathways and fail to reveal the global effects of infection on the host’s metabolism.…”

mentioning

confidence: 99%

Metabolomic Profiling of Mice Serum during Toxoplasmosis Progression Using Liquid Chromatography-Mass Spectrometry

Zhou

Elsheikha

et al. 2016

Sci Rep

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Better understanding of the molecular changes associated with disease is essential for identifying new routes to improved therapeutics and diagnostic tests. The aim of this study was to investigate the dynamic changes in the metabolic profile of mouse sera during T. gondii infection. We carried out untargeted metabolomic analysis of sera collected from female BALB/c mice experimentally infected with the T. gondii Pru strain (Genotype II). Serum samples were collected at 7, 14 and 21 day post infection (DPI) from infected and control mice and were subjected to liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS)-based global metabolomics analysis. Multivariate statistical analysis identified 79 differentially expressed metabolites in ESI+ mode and 74 in ESI− mode in sera of T. gondii-infected mice compared to the control mice. Further principal component analysis (PCA) and partial least squares-discrimination analysis (PLS-DA) identified 19 dysregulated metabolites (5 in ESI+ mode and 14 in ESI− mode) related to the metabolism of amino acids and energy metabolism. The potential utility of these metabolites as diagnostic biomarkers was validated through receiver operating characteristic (ROC) curve analysis. These findings provide putative metabolite biomarkers for future study and allow for hypothesis generation about the pathophysiology of toxoplasmosis.

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Parasite Manipulation of the Invariant Chain and the Peptide Editor H2-DM Affects Major Histocompatibility Complex Class II Antigen Presentation during Toxoplasma gondii Infection

Cited by 15 publications

References 82 publications

Toxoplasma gondii infection reduces serum progesterone levels and adverse effects at the maternal‐foetal interface

Toxoplasma gondii infection reduces serum progesterone levels and adverse effects at the maternal‐foetal interface

The Protozoan Parasite Toxoplasma gondii Selectively Reprograms the Host Cell Translatome

Metabolomic Profiling of Mice Serum during Toxoplasmosis Progression Using Liquid Chromatography-Mass Spectrometry

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