Clearance of a persistent picornavirus infection is associated with enhanced pro-apoptotic and cellular immune responses
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ABSTRACT:
PROVIDER: PRJNA408127 | ENA |
REPOSITORIES: ENA
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Project description:Immunomodulatory mechanisms associated with clearance versus persistence of foot-and-mouth disease virus (FMDV) in micro-dissected compartments of the bovine nasopharynx were investigated using qRT-PCR and whole transcriptome microarray. Analysis of tissue samples obtained by laser capture microdissection (LCM) during transitional and persistent phases of infection demonstrated significant differences in transcriptome profiles of animals that cleared infection versus those that became persistently infected carriers. The combined output of the analyses suggested that clearance of FMDV from the nasopharyngeal mucosa is associated with an activated cellular immune response. This was supported by induction of Th1-associated mediators and upregulation of multiple targets associated with activation of T cell-mediated cytotoxicity in tissues from animals that cleared infection. Contrastingly, the pattern of gene regulation in FMDV carriers during transitional and persistent phases of infection suggested inhibition of T cell activation and promotion of Th2 polarization. Regulation of genes associated with apoptosis or cellular proliferation suggested inhibition of apoptotic pathways and promotion of cellular proliferation associated with FMDV persistence while the opposite patterns were found in animals that cleared infection. The findings presented herein emphasize the critical importance of Th1-mediated cellular immunity for clearance of persistent FMDV infection. Additionally, the strong antibody-mediated immune response that is induced during acute infection may impair efficient clearance of intra-cellular virus, thereby promoting FMDV persistence. Thus, a critical balance between Th1 and Th2 -mediated immunity is essential for successful clearance of FMDV infection and should be considered for development of next-generation vaccines and antiviral products.
2017-12-19 | GSE104058 | GEO
Project description:Long-term persistent viral infections cause substantial morbidity and associated economic losses in human and veterinary contexts. Yet, the mechanisms associated with establishment of persistent infections are poorly elucidated. We investigated immunomodulatory mechanisms associated with clearance versus persistence of foot-and-mouth disease virus (FMDV) in micro-dissected compartments of the bovine nasopharynx by microarray. The use of laser-capture microdissection allowed elucidation of differential gene regulation within distinct anatomic compartments critical to FMDV infection. Analysis of samples from transitional and persistent phases of infection demonstrated significant differences in transcriptome profiles of animals that cleared infection versus those that became persistently infected carriers. Specifically, it was demonstrated that clearance of FMDV from the nasopharyngeal mucosa was associated with upregulation of targets associated with activation of T cell-mediated immunity. Contrastingly, gene regulation in FMDV carriers suggested inhibition of T cell activation and promotion of Th2 polarization. These findings were corroborated by immunofluorescence microscopy which demonstrated relative abundance of CD8+?T cells in the nasopharyngeal mucosa in association with clearance of FMDV. The findings presented herein emphasize that a critical balance between Th1 and Th2 -mediated immunity is essential for successful clearance of FMDV infection and should be considered for development of next-generation vaccines and antiviral products.
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2017-11-15 | GSE93820 | GEO
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Project description:Goal: Determine the role of microglia in the antiviral response during neurotropic picornavirus infection of C57BL/6J and SJL/J mice and whether absence of microglia would affect CD4 and CD8 T cell functions. Methods: Brains from C57BL/6J and SJL/J mice treated with PLX5622 (to deplete microlgia) or control diet were harvested at 6 days post TMEV-infection. CD4+ T cells and CD8+ T cells were obtained using Easy Sep Mouse CD4+ T cell isolation Kit and Easy Sep Mouse CD8+ T cell isolation Kit (Stemcell). RNA was obtained using RNeasy (QIAGEN) and Illumina TruSeq stranded RNA Kit with Ribo-Zero Gold was then utilized to prepare cDNA library for RNA-seq. Results: Our results demonstrate strain-specific effects of the CSF1R-microglia axis in the context of neurotropic viral infection as well as inherent differences in microglial antigen presentation and subsequent T cell crosstalk that contribute to susceptibility to neurotropic picornavirus infection.
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2019-08-01 | GSE134802 | GEO
Project description:The rapid elimination of dying neurons and non-functional synapses in the brain is carried out by microglia, the resident myeloid cells of the brain. Here we show that microglia clearance activity in the adult brain is regionally regulated and depends on the rate of neuronal attrition. Cerebellar, but not striatal or cortical, microglia exhibited high levels of basal clearance activity, which correlated with an elevated degree of cerebellar neuronal attrition. Exposing forebrain microglia to apoptotic cells activated gene expression programs supporting clearance activity. We provide evidence that the Polycomb repressive complex 2 (PRC2) epigenetically restricts the expression of genes that support clearance activity in striatal and cortical microglia. Loss of PRC2 led to the aberrant activation of a microglia clearance phenotype, which triggers changes in neuronal morphology and behavior. Our data highlight a key role of epigenetic mechanisms in preventing microglia-induced neuronal alterations that are frequently associated with neurodegenerative and psychiatric diseases.
2018-07-13 | GSE108356 | GEO