An in vitro model of intestinal infection reveals a developmentally regulated transcriptome of Toxoplasma sporozoites and a NF-κB-like signature in infected host cells

Guiton, Pascale S.; Sagawa, Janelle M.; Fritz, Heather M.; Boothroyd, John C.

doi:10.1371/journal.pone.0173018

Cited by 18 publications

(16 citation statements)

References 75 publications

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“…In the present study, as infection progressed, the expression of MHC I genes was elevated at 72 and 96 hpi, indicating that the cats may have mounted a CTL response, mediated by MHC I, to limit replication of the parasite. Infecting cultured rat-intestinal epithelial cells with mature sporozoites, induced an elevated expression of genes associated with tumor necrosis factor alpha (TNFα) signaling, via NF-κB [44]. This transcriptomic change was not observed in our study, suggesting that anti-T. gondii intestinal immunity can vary between different hosts and different parasite stages, and based on whether the infection was established under in vitro or in vivo conditions.…”

Section: Discussioncontrasting

confidence: 65%

Transcriptomic insights into the early host-pathogen interaction of cat intestine with Toxoplasma gondii

et al. 2018

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BackgroundAlthough sexual reproduction of the parasite Toxoplasma gondii exclusively occurs in the cat intestine, knowledge about the alteration of gene expression in the intestine of cats infected with T. gondii is still limited. Here, we investigated the temporal transcriptional changes that occur in the cat intestine during T. gondii infection.MethodsCats were infected with 100 T. gondii cysts and their intestines were collected at 6, 12, 18, 24, 72 and 96 hours post-infection (hpi). RNA sequencing (RNA-Seq) Illumina technology was used to gain insight into the spectrum of genes that are differentially expressed due to infection. Quantitative RT-PCR (qRT-PCR) was also used to validate the level of expression of a set of differentially expressed genes (DEGs) obtained by sequencing.ResultsOur transcriptome analysis revealed 2363 DEGs that were clustered into six unique patterns of gene expression across all the time points after infection. Our analysis revealed 56, 184, 404, 508, 400 and 811 DEGs in infected intestines compared to uninfected controls at 6, 12, 18, 24, 72 and 96 hpi, respectively. RNA-Seq results were confirmed by qRT-PCR. DEGs were mainly enriched in catalytic activity and metabolic process based on gene ontology enrichment analysis. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that transcriptional changes in the intestine of infected cats evolve over the course of infection, and the largest difference in the enriched pathways was observed at 96 hpi. The anti-T. gondii defense response of the feline host was mediated by Major Histocompatibility Complex class I, proteasomes, heat-shock proteins and fatty acid binding proteins.ConclusionsThis study revealed novel host factors, which may be critical for the successful establishment of an intracellular niche during T. gondii infection in the definitive feline host.Electronic supplementary materialThe online version of this article (10.1186/s13071-018-3179-8) contains supplementary material, which is available to authorized users.

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Section: Discussioncontrasting

confidence: 65%

Transcriptomic insights into the early host-pathogen interaction of cat intestine with Toxoplasma gondii

et al. 2018

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“…Therefore, successful infection of the host intestine is essential for subsequent parasite dissemination to different tissues. Others have showed that in vitro infection of rat intestinal epithelial cells can trigger an inflammatory response characterized by Tumor Necrosis Factor alpha (TNFα) signaling via NF-κB ( 46 ). However, feline host factors that are influenced by intestinal infection remain largely unknown.…”

Section: Discussionmentioning

confidence: 99%

Acute Toxoplasma Gondii Infection in Cats Induced Tissue-Specific Transcriptional Response Dominated by Immune Signatures

et al. 2018

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RNA-sequencing was used to detect transcriptional changes in six tissues of cats, seven days after T. gondii infection. A total of 737 genes were differentially expressed (DEGs), of which 410 were up-regulated and 327 were down-regulated. The liver exhibited 151 DEGs, lung (149 DEGs), small intestine (130 DEGs), heart (123 DEGs), brain (104 DEGs), and spleen (80 DEGs)-suggesting tissue-specific transcriptional patterns. Gene ontology and KEGG analyses identified DEGs enriched in immune pathways, such as cytokine-cytokine receptor interaction, Jak-STAT signaling pathway, NOD-like receptor signaling pathway, NF-kappa B signaling pathway, MAPK signaling pathway, T cell receptor signaling pathway, and the cytosolic DNA sensing pathway. C-X-C motif chemokine 10 (CXCL10) was involved in most of the immune-related pathways. PI3K/Akt expression was down-regulated in all tissues, except the spleen. The genes for phosphatase, indoleamine 2,3-dioxygenase, Hes Family BHLH Transcription Factor 1, and guanylate-binding protein 5, playing various roles in immune defense, were co-expressed across various feline tissues. Multivariate K-means clustering analysis produced seven gene clusters featuring similar gene expression patterns specific to individual tissues, with lung tissue cluster having the largest number of DEGs. These findings suggest the presence of a broad immune defense mechanism across various tissues in cats against acute T. gondii infection.

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“…The risk for intubation should be assessed carefully as it is associated with higher mortality. The introduction of non-invasive tests, notably those based on next-generation sequencing (NGS), transcriptomics, and proteomics, may reduce the need for FOB/BAL [12][13][14][15][16]. Updated research is needed,…”

Section: General Considerationsmentioning

confidence: 99%

Diagnosis of severe respiratory infections in immunocompromised patients

et al. 2020

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An increasing number of critically ill patients are immunocompromised. Acute hypoxemic respiratory failure (ARF), chiefly due to pulmonary infection, is the leading reason for ICU admission. Identifying the cause of ARF increases the chances of survival, but may be extremely challenging, as the underlying disease, treatments, and infection combine to create complex clinical pictures. In addition, there may be more than one infectious agent, and the pulmonary manifestations may be related to both infectious and non-infectious insults. Clinically or microbiologically documented bacterial pneumonia accounts for one-third of cases of ARF in immunocompromised patients. Early antibiotic therapy is recommended but decreases the chances of identifying the causative organism(s) to about 50%. Viruses are the second most common cause of severe respiratory infections. Positive tests for a virus in respiratory samples do not necessarily indicate a role for the virus in the current acute illness. Invasive fungal infections (Aspergillus, Mucorales, and Pneumocystis jirovecii) account for about 15% of severe respiratory infections, whereas parasites rarely cause severe acute infections in immunocompromised patients. This review focuses on the diagnosis of severe respiratory infections in immunocompromised patients. Special attention is given to newly validated diagnostic tests designed to be used on non-invasive samples or bronchoalveolar lavage fluid and capable of increasing the likelihood of an early etiological diagnosis.

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An in vitro model of intestinal infection reveals a developmentally regulated transcriptome of Toxoplasma sporozoites and a NF-κB-like signature in infected host cells

Cited by 18 publications

References 75 publications

Transcriptomic insights into the early host-pathogen interaction of cat intestine with Toxoplasma gondii

Transcriptomic insights into the early host-pathogen interaction of cat intestine with Toxoplasma gondii

Acute Toxoplasma Gondii Infection in Cats Induced Tissue-Specific Transcriptional Response Dominated by Immune Signatures

Diagnosis of severe respiratory infections in immunocompromised patients

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