scholarly journals Modulation of the Bovine Trophoblastic Innate Immune Response by Brucella abortus

2008 ◽  
Vol 76 (5) ◽  
pp. 1897-1907 ◽  
Author(s):  
Alcina V. Carvalho Neta ◽  
Ana P. R. Stynen ◽  
Tatiane A. Paixão ◽  
Karina L. Miranda ◽  
Fabiana L. Silva ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Innate Immune Response ◽  
Brucella Abortus ◽  
Innate Immune ◽  
Chemokine Expression ◽  
Trophoblastic Cells ◽  
Proinflammatory Mediators ◽  
Reverse Transcription Pcr ◽  
Cytokines And Chemokines

ABSTRACT Brucellosis is still a widespread zoonotic disease. Very little is known about the interaction between Brucella abortus and trophoblastic cells, which is essential for better understanding the pathogenesis of the Brucella-induced placentitis and abortion, a key event for transmission of the disease. The goal of this study was to evaluate the profile of gene expression by bovine trophoblastic cells during infection with B. abortus. Explants of chorioallantoic membranes were inoculated with B. abortus strain 2308. Microarray analysis was performed at 4 h after infection, and expression of cytokines and chemokines by trophoblastic cells was assessed by real-time reverse transcription-PCR at 6 and 12 h after inoculation. In addition, cytokine and chemokine expression in placentomes from experimentally infected cows was evaluated. Expression of proinflammatory genes by trophoblastic cells was suppressed at 4 h after inoculation, whereas a significant upregulation of CXC chemokines, namely, CXCL6 (GCP-2) and CXCL8 (interleukin 8), was observed at 12 but not at 6 h after inoculation. Placentomes of experimentally infected cows had a similar profile of chemokine expression, with upregulation of CXCL6 and CXCL8. Our data indicate that B. abortus modulates the innate immune response by trophoblastic cells, suppressing the expression of proinflammatory mediators during the early stages of infection that is followed by a delayed and mild expression of proinflammatory chemokines, which is similar to the profile of chemokine expression in the placentomes of experimentally infected cows. This trophoblastic response is likely to contribute to the pathogenesis of B. abortus-induced placentitis.

scholarly journals Gene expression variability across cells and species shapes innate immunity

2017 ◽  
Author(s):  
Tzachi Hagai ◽  
Xi Chen ◽  
Ricardo J Miragaia ◽  
Tomás Gomes ◽  
Raghd Rostom ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Innate Immunity ◽  
Innate Immune Response ◽  
Innate Immune ◽  
First Line ◽  
Expression Variability ◽  
Cytokines And Chemokines ◽  
Cell To Cell Variability ◽  
Unique Expression Pattern

SummaryAs the first line of defence against pathogens, cells mount an innate immune response, which is highly variable from cell to cell. The response must be potent yet carefully controlled to avoid self-damage. How these constraints have shaped the evolution of innate immunity remains poorly understood. Here, we characterise this programme’s transcriptional divergence between species and expression variability across cells. Using bulk and single-cell transcriptomics in primate and rodent fibroblasts challenged with an immune stimulus, we reveal a striking architecture of the innate immune response. Rapidly diverging genes, including cytokines and chemokines, also vary across cells and have distinct promoter structures. Conversely, genes involved in response regulation, such as transcription factors and kinases, are conserved between species and display low cell-to-cell variability. We suggest that this unique expression pattern, observed across species and conditions, has evolved as a mechanism for fine-tuned regulation, to achieve an effective but balanced response.

scholarly journals REDIportal: millions of novel A-to-I RNA editing events from thousands of RNAseq experiments

2020 ◽  
Vol 49 (D1) ◽  
pp. D1012-D1019 ◽  
Author(s):  
Luigi Mansi ◽  
Marco Antonio Tangaro ◽  
Claudio Lo Giudice ◽  
Tiziano Flati ◽  
Eli Kopel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Comparative Genomics ◽  
Rna Editing ◽  
Innate Immune Response ◽  
Transcriptome Sequencing ◽  
Regulation Of Gene Expression ◽  
Innate Immune ◽  
Neurotransmitter Receptors ◽  
Eukaryotic Organisms

Abstract RNA editing is a relevant epitranscriptome phenomenon able to increase the transcriptome and proteome diversity of eukaryotic organisms. ADAR mediated RNA editing is widespread in humans in which millions of A-to-I changes modify thousands of primary transcripts. RNA editing has pivotal roles in the regulation of gene expression or modulation of the innate immune response or functioning of several neurotransmitter receptors. Massive transcriptome sequencing has fostered the research in this field. Nonetheless, different aspects of the RNA editing biology are still unknown and need to be elucidated. To support the study of A-to-I RNA editing we have updated our REDIportal catalogue raising its content to about 16 millions of events detected in 9642 human RNAseq samples from the GTEx project by using a dedicated pipeline based on the HPC version of the REDItools software. REDIportal now allows searches at sample level, provides overviews of RNA editing profiles per each RNAseq experiment, implements a Gene View module to look at individual events in their genic context and hosts the CLAIRE database. Starting from this novel version, REDIportal will start collecting non-human RNA editing changes for comparative genomics investigations. The database is freely available at http://srv00.recas.ba.infn.it/atlas/index.html.

Transient membrane recruitment of IRAK-1 in response to LPS and IL-1β requires TNF R1

2008 ◽  
Vol 295 (2) ◽  
pp. C313-C323 ◽  
Author(s):  
Angelia Lockett ◽  
Mark G. Goebl ◽  
Maureen A. Harrington
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Plasma Membrane ◽  
Innate Immune Response ◽  
Cellular Response ◽  
Interleukin 1 ◽  
Innate Immune ◽  
Variable Response ◽  
Membrane Recruitment ◽  
Tnf Α

The transcription factor NF-κB is an essential regulator of the innate immune response that functions as the first line of defense against infections. Activation of the innate immune response by bacterial lipopolysaccharide (LPS) triggers production of tumor necrosis factor-α (TNF-α) followed by interleukin-1 (IL-1). The IL-1 receptor associated kinase-1 (IRAK-1) is an integral component of the LPS, TNF-α, and IL-1 signaling pathways that regulate NF-κB. Thus we hypothesized that IRAK-1 coordinates cellular NF-κB responses to LPS, TNF-α, and IL-1. In contrast to TNF-α where IRAK-1 subcellular localization does not change, treatment with LPS or IL-1 leads to a loss in cytoplasmic IRAK-1 with a coordinate increase in plasma membrane associated modified IRAK-1. In fibroblasts lacking the type 1 TNF-α receptor (TNF R1), IRAK-1 turnover is altered and modification of IRAK-1 in the plasma membrane is decreased in response to LPS and IL-1, respectively. When NF-κB controlled gene expression is measured, fibroblasts lacking TNF R1 are hyperresponsive to LPS, whereas a more variable response to IL-1 is seen. Further analysis of the LPS response revealed that plasma membrane-associated IRAK-1 is found in Toll 4, IL-1, and TNF R1-containing complexes. The data presented herein suggest a model whereby the TNF R1-IRAK-1 interaction integrates the cellular response to LPS, TNF-α, and IL-1, culminating in a cell poised to activate TNF-α-dependent NF-κB controlled gene expression. In the absence of TNF R1-dependent events, exposure to LPS or IL-1 leads to hyperactivation of the inflammatory response.

scholarly journals Acute Simian Varicella Virus Infection Causes Robust and Sustained Changes in Gene Expression in the Sensory Ganglia

2016 ◽  
Vol 90 (23) ◽  
pp. 10823-10843 ◽  
Author(s):  
Nicole Arnold ◽  
Thomas Girke ◽  
Suhas Sureshchandra ◽  
Ilhem Messaoudi
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
T Cells ◽  
Virus Infection ◽  
Innate Immune Response ◽  
Rhesus Macaques ◽  
Innate Immune ◽  
Sensory Ganglia ◽  
Simian Varicella Virus ◽  
Varicella Virus

ABSTRACTPrimary infection with varicella-zoster virus (VZV), a neurotropic alphaherpesvirus, results in varicella. VZV establishes latency in the sensory ganglia and can reactivate later in life to cause herpes zoster. The relationship between VZV and its host during acute infection in the sensory ganglia is not well understood due to limited access to clinical specimens. Intrabronchial inoculation of rhesus macaques with simian varicella virus (SVV) recapitulates the hallmarks of VZV infection in humans. We leveraged this animal model to characterize the host-pathogen interactions in the ganglia during both acute and latent infection by measuring both viral and host transcriptomes on days postinfection (dpi) 3, 7, 10, 14, and 100. SVV DNA and transcripts were detected in sensory ganglia 3 dpi, before the appearance of rash. CD4 and CD8 T cells were also detected in the sensory ganglia 3 dpi. Moreover, lung-resident T cells isolated from the same animals 3 dpi also harbored SVV DNA and transcripts, suggesting that T cells may be responsible for trafficking SVV to the ganglia. Transcriptome sequencing (RNA-Seq) analysis showed that cessation of viral transcription 7 dpi coincides with a robust antiviral innate immune response in the ganglia. Interestingly, a significant number of genes that play a critical role in nervous system development and function remained downregulated into latency. These studies provide novel insights into host-pathogen interactions in the sensory ganglia during acute varicella and demonstrate that SVV infection results in profound and sustained changes in neuronal gene expression.IMPORTANCEMany aspects of VZV infection of sensory ganglia remain poorly understood, due to limited access to human specimens and the fact that VZV is strictly a human virus. Infection of rhesus macaques with simian varicella virus (SVV), a homolog of VZV, provides a robust model of the human disease. Using this model, we show that SVV reaches the ganglia early after infection, most likely by T cells, and that the induction of a robust innate immune response correlates with cessation of virus transcription. We also report significant changes in the expression of genes that play an important role in neuronal function. Importantly, these changes persist long after viral replication ceases. Given the homology between SVV and VZV, and the genetic and physiological similarities between rhesus macaques and humans, our results provide novel insight into the interactions between VZV and its human host and explain some of the neurological consequences of VZV infection.

scholarly journals Vaccinia virus immune evasion: mechanisms, virulence and immunogenicity

2013 ◽  
Vol 94 (11) ◽  
pp. 2367-2392 ◽  
Author(s):  
Geoffrey L. Smith ◽  
Camilla T. O. Benfield ◽  
Carlos Maluquer de Motes ◽  
Michela Mazzon ◽  
Stuart W. J. Ember ◽  
...  
Keyword(s):  
Immune Response ◽  
Vaccinia Virus ◽  
Innate Immune Response ◽  
Immune Evasion ◽  
Mammalian Cells ◽  
Innate Immune ◽  
Gene Encoding ◽  
Cytokines And Chemokines ◽  
Host Innate Immune Response ◽  
New Hosts

Virus infection of mammalian cells is sensed by pattern recognition receptors and leads to an innate immune response that restricts virus replication and induces adaptive immunity. In response, viruses have evolved many countermeasures that enable them to replicate and be transmitted to new hosts, despite the host innate immune response. Poxviruses, such as vaccinia virus (VACV), have large DNA genomes and encode many proteins that are dedicated to host immune evasion. Some of these proteins are secreted from the infected cell, where they bind and neutralize complement factors, interferons, cytokines and chemokines. Other VACV proteins function inside cells to inhibit apoptosis or signalling pathways that lead to the production of interferons and pro-inflammatory cytokines and chemokines. In this review, these VACV immunomodulatory proteins are described and the potential to create more immunogenic VACV strains by manipulation of the gene encoding these proteins is discussed.

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