Host-responses to Poxvirus-infected macrophages
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PROVIDER: PRJNA494077 | ENA |
REPOSITORIES: ENA
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Project description:Evolutionarily successful poxviruses presented effective and diverse strategies to circumvent or overcome host defense mechanisms. Poxviruses encode many immunoregulatory proteins to evade host immunity for a productive infection and unique means of inhibiting DNA-sensing dependent type 1 interferon (IFN-I) responses is anticipated due to the biology of its dsDNA genome in nature and an exclusive cytoplasmic life cycle. We found the key DNA sensing inhibition by poxvirus infection was dominant during the early stage of poxvirus infection independent from DNA replication. In an effort of identifying poxvirus novel means to subdue antiviral proinflammatory responses e.g., IFN-I response, we focused on the function of one early gene that is the known host range determinant from the highly conserved poxvirus host range C7L superfamily, myxoma virus (MYXV) M062. Host range factors are unique features of poxviruses that determine the species and cell type tropism. Almost all sequenced mammalian poxviruses retain at least one homologue of the poxvirus host range C7L superfamily. In MYXV, a rabbit specific poxvirus, the dominant and broad-spectrum host range determinant of the C7L superfamily is the M062R gene. M062R gene product is essential for MYXV infection in almost all cells tested from different mammalian species and specifically inhibits the function of host Sterile α Motif Domain-containing 9 (SAMD9), as M062R-null (ΔM062R) MYXV causes abortive infection in a SAMD9-dependend manner. In this study we investigated the immunostimulatory property of the ΔM062R. We found that the replication-defective ΔM062R infection activated host DNA sensing pathway in the cGAS dependent fashion and knocking down SAMD9 expression attenuated proinflammatory responses. Moreover, transcriptomic analyses showed a unique feature of host gene expression landscape that is different from dsDNA stimulated inflammatory state. This study built a link between the anti-neoplastic SAMD9 and the regulation of the innate immune responses.
2022-02-14 | GSE196608 | GEO
Project description:Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, a chronic granulomatous disease. Mtb is mostly restricted to humans and seldom causes disease in animals. M. bovis (Mbv) on the other hand causes tuberculosis in cows (bovine tuberculosis) and several wild animals. Each of these pathogens therefore has unique host adaptations and the host- and pathogen-specific factors driving this differential tropism still remain largely unknown. Here we profiled the secretomes of Mtb- and Mbv-infected bovine macrophages to characterise host-specific responses to each pathogen.
2021-03-11 | PXD017949 | Pride
Project description:Highly pathogenic Zaire ebolavirus (EBOV) infection is associated with a dysregulated immune response and high levels of cytokines and chemokines are observed in fatal human cases. . In stark contrast Reston ebolavirus (RESTV) might be non-pathogenic for humans yet the underlying mechanisms determining pathogenicity for different Ebola viruses are not understood. In this study we investigate antiviral immune responses in EBOV- and RESTV- infected primary human monocyte-derived macrophages (MDM). We provide evidence that increased pathogenicity of the highly pathogenic EBOV is associated with a strong activation of host responses from infected MDM. The observed cytokine response after EBOV infection is strikingly similar to LPS-mediated immune signatures however EBOV caused significant induction of the interferon response in addition. In contrast we show that the low pathogenic RESTV fails to elicit significant immune responses in infected MDM. These results demonstrate a correlation of pathogenicity and excessive MDM activation for different Ebola virus species. Interaction of the viral glycoprotein (GP) with Toll-like receptor 4 (TLR4) leading to activation of NF_B signaling is responsible for this effect rather than differences in replication or blocking of immune signaling. We demonstrate that inhibition of TLR4 is able to abolish EBOV-GP mediated NF_B activation which might offer the possibility to develop targeted treatments for EBOV limiting the extreme immune response that seems to be detrimental to the host.
2016-12-31 | GSE84188 | GEO
Project description:We used the microarray data to analyse the host cell responses on mouse macrophages infected with the three Influenza A viruses The global expression analysis showed increased expression changes in H5N3 infected mouse macrophages compared to H5N2/F118 and H1N1/WSN
2017-06-23 | GSE86446 | GEO
Project description:Host macrophage transcriptional responses to intracellular pathogens remain poorly characterized. We screened transcriptional enhancers engaged in response to M. tuberculosis (Mtb) infection by ChIPseq analysis of histone H3 lysine 4 monomethylation (H3K4me1). De novo monomethylation during infection was associated with genes implicated in host defense and apoptosis. These regions were enriched for binding sites for ETS transcription factor family members and response elements for nuclear receptors, including liver X receptors (LXRs) and peroxisomal proliferator activated receptors (PPARs), many of which were encompassed by transposable elements. LXRa expression was strongly induced by infection, whereas that of PPARs was unaffected. LXR DNA binding and NCoR corepressor recruitment increased proportionately in infected cells but coactivator association was unchanged, consistent with a lack of induction of endogenous agonists. However, treatment of infected cells with LXR agonist T0901317 strongly increased coactivator recruitment and induced a gene expression program characterized by enhanced innate immune signaling and lipid metabolism. Remarkably, T0901317 treatment selectively induced apoptosis in infected macrophages, and was accompanied by Mtb death, reducing mycobacterial burden 18-fold relative to vehicle 5d after infection. These studies define macrophage transcriptional responses to Mtb infection, and suggest that tissue-specific LXRa agonists may be efficacious in clinical management of tuberculosis.
2015-10-15 | E-MTAB-3192 | biostudies-arrayexpress
Project description:Toxoplasma gondii is a ubiquitous protozoan pathogen able to infect both mammalian and avian hosts. Surprisingly, just three strains appear to account for the majority of isolates from Europe and N. America. To test the hypothesis that strain divergence might be driven by differences between mammalian and avian response to infection, we examine in vitro strain-dependent host responses in a representative avian host, the chicken. Chicken embryonic fibroblasts were cultivated in vitro and infected with different strains of Toxoplasma gondii; host transcriptional responses were then analyzed at 24 hours post-infection.
2011-05-27 | E-GEOD-29563 | biostudies-arrayexpress
Project description:Background: Mycobacterium avium is an opportunistic pathogen that requires complex multidrug treatment. Macrolides, like clarithromycin, are the cornerstone of treatment, but even macrolide-based treatment regimens have suboptimal outcomes. Combining transcriptomic profiling of macrophages and mycobacteria in an in vitro infection model may increase our understanding of the host-pathogen interaction and the effect of antibiotic treatment. Methods: To investigate the molecular interplay between pathogen and host, we developed an optimized protocol for dual RNA-sequencing of human monocyte-derived macrophages infected with M. avium. Results: Upon phagocytosis, host defense processes including immune activation and pathogen recognition were upregulated, while M. avium upregulated expression of PE/PPE genes, which are important for immune recognition. Clarithromycin did not affect gene regulation of the host; the effect of clarithromycin on M. avium gene expression was very different in RPMI compared to intracellular mycobacteria, likely due to the influence of the host environment on expression of the important regulatory WhiB genes. Conclusions These data identify the distinct stress responses of M. avium upon infection and clarithromycin treatment and underline the importance of taking the intracellular localization and interaction with the host into account when studying antibiotics against intracellular pathogens.
2024-01-01 | GSE213117 | GEO
Project description:Porcine macrophages: ASFV-infected vs. mock-infected
| PRJNA549440 | ENA
Project description:Purpose: The purpose of this study was to simulataneously examine the host and fungal pathogen transcriptional profiles of four distinct infection fates during macrophage and Candida albicans interactions Methods: Membrane stained (Deep Red),primary, bone marrow derived, murine macrophages and Candida albicans expressing GFP and mCherry were exposed to each other over a four hour time course. Samples were collected at 0, 1, 2 and 4 hours and sorted for four infection subpopulations: 1. Macrophages which phagocytosed live C. albicans (GFP+ /mCherry+ /Deep Red +), 2. Macrophages which phagocytosed dead C. albicans (GFP- /mCherry+ /Deep Red +), 3. Uninfected macrophages(GFP- /mCherry- /Deep Red +) and 4. Unengulfed C. albicans (GFP+ /mCherry + /Deep Red -). Unexposed controls were also collected for some time points (i.e. macrophages never exposed to C. albicans and C. albicans never exposed to macrophages). Single macrophages infected with live or dead C. albicans were also sorted. Smart-seq2 was used to create libraries for both infection subpopulation and single, infected cell samples that were sequenced on Illumina’s Miseqand Nextseq. Basic quality assessment of Illumina reads and sample demultiplexing was done with Picard version 1.107 and Trimmomatic. Samples profiling exclusively the mouse transcriptional response were aligned to the mouse transcriptome generated from the v. Dec. 2011 GRCm38/mm10 and a collection of mouse rRNA sequences from the UCSC genome website. Samples profiling exclusively the yeast transcriptional response were aligned to the C. albicans transcriptome strain SC5314 version A21-s02-m09-r10 downloaded from Candida Genome Database. Samples containing both macrophages and C. albicans were aligned to a “composite transcriptome” made by combining the mouse transcriptome and C. albicans transcriptomes described above and alignment was done via BWA (version 0.7.10-r789.) Multi-reads (reads that aligned to both host and pathogen transcripts) were discarded. Then, each host or pathogen sample file were aligned to its corresponding reference using Bowtie2 and RSEM (v.1.2.21). Transcript abundance was estimated using transcripts per million (TPM). For subpopulation samples, TPM was calculated using edgeR, all as implemented in the Trinity package version 2.1.. Genes were considered differentially expressed only if they had a 4-fold change difference (> 4 FC) in TPM values and a false discovery rate below or equal to 0.001 (FDR < 0.001), unless specified otherwise. For single macrophages infected with C. albicans, samples were aligned to the combined transcriptome as described above and RSEM was used to calculate TPM. Results: We were able to simultaneously measure the host and fungal pathogen transcriptional profiles of four distinct infection fates during macrophage and Candida albicans interactions Conclusions: Our study represents an analysis of both distinct infection populations of macrophages and fungus.
2018-03-12 | GSE111731 | GEO
Project description:Toxoplasma gondii is a ubiquitous protozoan pathogen able to infect both mammalian and avian hosts. Surprisingly, just three strains appear to account for the majority of isolates from Europe and N. America. To test the hypothesis that strain divergence might be driven by differences between mammalian and avian response to infection, we examine in vitro strain-dependent host responses in a representative avian host, the chicken. To identify parasite drivers of strain-dependent host response, QTL mapping was used; analysis revealed a locus on Toxoplasma chromosome VIIb. To determine whether this was the parasite gene ROP16, array analysis was performed on chicken embryonic fibroblasts infected with Type I parasites and ROP16-KO parasites (of a Type I background). Chicken embryonic fibroblasts were cultivated in vitro and infected with either Type I (RH) parasites or Type I ROP16-KO parasites; ROP16-dependent host transcriptional responses were then analyzed at 5 hours post-infection.
2011-05-27 | E-GEOD-29564 | biostudies-arrayexpress