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Innate Immune Sensing of HIV-1 by Dendritic Cells

HIV-1-specific antibodies and CD8+ cytotoxic T cells are detected in most HIV-1-infected people, yet HIV-1 infection is not eradicated. Contributing to the failure to mount a sterilizing immune response may be the inability of antigen-presenting dendritic cells (DCs) to sense HIV-1 during acute infection, and thus the inability to effectively prime naive, HIV-1-specific T cells.

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Host Cell & Pathogen Interactions
Strategies of Microbial Virulence and Host Defense
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Rescooped by Ken Yaw Agyeman-Badu from immunology
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The Immunoreceptor TIGIT Regulates Antitumor and Antiviral CD8+ T Cell Effector Function: Cancer Cell

The Immunoreceptor TIGIT Regulates Antitumor and Antiviral CD8+ T Cell Effector Function: Cancer Cell | Host Cell & Pathogen Interactions | Scoop.it
RT @genentech: New paper from our scientists in @Cancer_Cell shows how TIGIT may be potential #immunotherapy target http://t.co/FswC0GF9YB

 

Highlights

 

•Human and murine tumor-infiltrating CD8+ T cells express high levels of TIGIT•Antibody coblockade of TIGIT and PDL1 elicits tumor rejection in preclinical models•TIGIT selectively limits the effector function of chronically stimulated CD8+T cells•TIGIT interacts with CD226 in cis and disrupts CD226 homodimerization

 

Summary

Tumors constitute highly suppressive microenvironments in which infiltrating T cells are “exhausted” by inhibitory receptors such as PD-1. Here we identify TIGIT as a coinhibitory receptor that critically limits antitumor and other CD8+ T cell-dependent chronic immune responses. TIGIT is highly expressed on human and murine tumor-infiltrating T cells, and, in models of both cancer and chronic viral infection, antibody coblockade of TIGIT and PD-L1 synergistically and specifically enhanced CD8+ T cell effector function, resulting in significant tumor and viral clearance, respectively. This effect was abrogated by blockade of TIGIT’s complementary costimulatory receptor, CD226, whose dimerization is disrupted upon direct interaction with TIGIT in cis. These results define a key role for TIGIT in inhibiting chronic CD8+ T cell-dependent responses.


Via Krishan Maggon , Gilbert Faure au nom de l'ASSIM
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Krishan Maggon 's curator insight, December 13, 1:32 AM

Cancer Cell

 

The Immunoreceptor TIGIT Regulates Antitumor and Antiviral CD8+ T Cell Effector FunctionRobert J. Johnston, Laetitia Comps-Agrar, Jason Hackney, Xin Yu, Mahrukh Huseni, Yagai Yang, Summer Park, Vincent Javinal, Henry Chiu, Bryan Irving,Dan L. Eaton, Jane L. Grogan DOI: http://dx.doi.org/10.1016/j.ccell.2014.10.018
Gilbert Faure au nom de l'ASSIM's curator insight, December 13, 2:28 AM

TIGIT?

http://en.wikipedia.org/wiki/TIGIT

Rescooped by Ken Yaw Agyeman-Badu from Virology and Bioinformatics from Virology.ca
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Human Viruses and Cancer

Human Viruses and Cancer | Host Cell & Pathogen Interactions | Scoop.it
To date, seven viruses have been consistently linked to different types of human cancer, and infections are estimated to account for up to 20% of all cancer cases worldwide.

Via Chris Upton + helpers
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pH-Dependent entry of chikungunya virus fusion into mosquito cells

Millions of human infections caused by arthropod-borne pathogens are initiated by the feeding of an infected mosquito on a vertebrate. However, interactions between the viruses and the mosquito vector, which facilitates successful infection and transmission of virus to a subsequent vertebrate host, are still not fully understood.
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E5564 inhibits immunosuppressive cytokine IL-10 induction promoted by HIV-1 Tat protein

In HIV-1 infected patients, production of interleukin-10 (IL-10), a highly immunosuppressive cytokine, is associated with progression of infection toward AIDS. HIV-1 Tat protein, by interacting with TLR4-MD2 at the membrane level, induces IL-10 production by primary human monocytes and macrophages. In the present study we evaluated the effect of the TLR4 antagonist Eritoran tetrasodium (E5564) on HIV-1 Tat-induced IL-10 production.
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Immune Checkpoint Inhibitors for Renal Cell Carcinoma - Targeted Oncology

Immune Checkpoint Inhibitors for Renal Cell Carcinoma - Targeted Oncology | Host Cell & Pathogen Interactions | Scoop.it
It is estimated that 1 in 63 individuals in the United States will develop renal cell carcinoma (RCC), making it among the most common cancers in the country.

Via Gilbert Faure au nom de l'ASSIM
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Gilbert Faure au nom de l'ASSIM's curator insight, November 27, 1:28 PM

Binding of PD-1 to B7-H1 and B7-DC inhibits signaling via phosphatidylinositol-3 kinase and its downstream target, AKT. This inhibition leads to downstream events responsible for decreased T-cell proliferation and survival. It also decreases protein synthesis in T cells and cytokine production.3 Therapies based on monoclonal antibodies directed against PD1 and its ligands (immune checkpoint blockade) are emerging as novel therapeutic options for patients with various solid tumors as well as hematologic malignancies, including RCC. Checkpoint inhibitors in RCC will be the subject of this review. - See more at: http://www.targetedonc.com/publications/targeted-therapies-cancer/2014/october-2014/Immune-Checkpoint-Inhibitors-for-Renal-Cell-Carcinoma#sthash.BlDdXafS.dpuf

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Small Things Considered: Why CRISPR Doesn't Work in E. coli

Small Things Considered: Why CRISPR Doesn't Work in E. coli | Host Cell & Pathogen Interactions | Scoop.it
by Elio | We received this query: »I enjoyed the article on your blog 'Six Questions About CRISPRs' by Merry Youle. I am an ex-lambdologist, having quit phage lambda in the early 70s and moved to GM-plants. There is one thing about CRISPR that I do not understand: Why did lambdologists not find CRISPR?
They found phage...
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Atypical MHC class II-expressing antigen-presenting cells: can anything replace a dendritic cell?

Atypical MHC class II-expressing antigen-presenting cells: can anything replace a dendritic cell? | Host Cell & Pathogen Interactions | Scoop.it

Dendritic cells, macrophages and B cells are regarded as the classical antigen-presenting cells of the immune system. However, in recent years, there has been a rapid increase in the number of cell types that are suggested to present antigens on MHC class II molecules to CD4+ T cells. In this Review, we describe the key characteristics that define an antigen-presenting cell by examining the functions of dendritic cells. We then examine the functions of the haematopoietic cells and non-haematopoietic cells that can express MHC class II molecules and that have been suggested to represent 'atypical' antigen-presenting cells. We consider whether any of these cell populations can prime naive CD4+ T cells and, if not, question the effects that they do have on the development of immune responses.


Via Krishan Maggon , Gilbert Faure au nom de l'ASSIM
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Krishan Maggon 's curator insight, November 15, 9:22 AM
Atypical MHC class II-expressing antigen-presenting cells: can anything replace a dendritic cell?Taku Kambayashi& Terri M. LauferAffiliationsCorresponding authorNature Reviews Immunology 14, 719–730 (2014) doi:10.1038/nri3754Published online 17 October 2014
Gilbert Faure au nom de l'ASSIM's curator insight, November 16, 1:09 PM

and epithelial cells in autoimmunity

Rescooped by Ken Yaw Agyeman-Badu from Virology and Bioinformatics from Virology.ca
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Host-Specific Parvovirus Evolution in Nature Is Recapitulated by In Vitro Adaptation to Different Carnivore Species

Host-Specific Parvovirus Evolution in Nature Is Recapitulated by In Vitro Adaptation to Different Carnivore Species | Host Cell & Pathogen Interactions | Scoop.it
From molecules to physiology
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Influenza A virus uses the aggresome processing machinery for host cell entry

During cell entry, capsids of incoming influenza A viruses (IAVs) must be uncoated before viral ribonucleoproteins (vRNPs) can enter the nucleus for replication. After hemagglutinin-mediated membrane fusion in late endocytic vacuoles, the vRNPs and the matrix proteins dissociate from each other and disperse within the cytosol. Here, we found that for capsid disassembly, IAV takes advantage of the host cell’s aggresome formation and disassembly machinery. The capsids mimicked misfolded protein aggregates by carrying unanchored ubiquitin chains that activated a histone deacetylase 6 (HDAC6)–dependent pathway. The ubiquitin-binding domain was essential for recruitment of HDAC6 to viral fusion sites and for efficient uncoating and infection. That other components of the aggresome processing machinery, including dynein, dynactin, and myosin II, were also required suggested that physical forces generated by microtubule- and actin-associated motors are essential for IAV entry.


Via burkesquires, Mel Melendrez-Vallard
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The role of TGF-ß signaling and apoptosis in innate and adaptive im... - PubMed - NCBI

BMC Syst Biol. 2014 Oct 24;8(1):116. [Epub ahead of print]
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Inhibition of cytoplasmic mRNA stress gran... [Cell Host Microbe. 2007] - PubMed - NCBI

PubMed comprises more than 23 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
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Rescooped by Ken Yaw Agyeman-Badu from SynBioFromLeukipposInstitute
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Thesis: Controlling gene expression in enterobacteriaceae: studies on sRNAs and strategies for synthetic biology


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Socrates Logos's curator insight, September 30, 3:55 PM

Dissertation presented to obtain the Master Degree in Molecular, Genetics and Biomedicine


by

Apura, Patrícia de Faria Pais


Transcriptional and post-transcriptional control of gene expression dictate the levels of proteins in the cell. Therefore the modulation of gene expression can have important consequences for biotechnological and/or pharmaceutical purposes. Among the types of cellular RNAs, small RNAs (sRNAs) have been an emerging class of bacterial gene expression regulators, which mostly act by base-pairing with one or more mRNA target(s) affecting their translation and/or their stability. Here, we focus on the study of SraL sRNA, more specifically in the validation of putative targets for this sRNA obtained in a previous transcriptomic analysis. Until now SraL was only shown to regulate the mRNA levels of Trigger Factor, an important protein chaperone. The information here reported give strong evidence for SraL involvement in the cysteine biosynthetic pathway, which requires further investigation. Nevertheless, our results could not provide a validation of those putative targets previously obtained by transcriptomic analyses. Optimization of protein expression requires not only an increase of the stability of mRNA transcripts but also an optimal behavior of function-encoding DNA segments, which are often context-dependent. Building on the work of others, we have designed a set of combinatorial promoters and 5’UTRs and evaluated their effects/outcomes using Superfolder GFP as reporter. Our data shows a clear variability of protein levels within our set of constructs. The highest levels of protein were associated with the implementation of an insulation sequence flanking the promoter region and the introduction of 5’ stabilizing structures at the mRNA level. Further investigation concerning the alteration of the rate of the mRNA decay by depletion of the function of participating nucleases, might constitute an advantageous approach. The knowledge collected will be extremely important to design robust modules which substantially increase protein production. This field is rapidly growing and much remains to be discovered about these important regulatory processes.

 


http://bit.ly/1qSyrSW

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Bacterial 'communication system' could be used to stop, kill cancer cells, study finds

Bacterial 'communication system' could be used to stop, kill cancer cells, study finds | Host Cell & Pathogen Interactions | Scoop.it
A molecule used as a communication system by bacteria can be manipulated to prevent cancer cells from spreading, a study has demonstrated. "During an infection, bacteria release molecules which allow them to 'talk' to each other," said the lead author of the study. "Depending on the type of molecule released, the signal will tell other bacteria to multiply, escape the immune system or even stop spreading."
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An Evolutionary Battle Against Bacteria

An Evolutionary Battle Against Bacteria | Host Cell & Pathogen Interactions | Scoop.it
A recent study illustrates how our ancestors evolved new defenses to starve meningitis-causing bacteria of the iron they need to grow.
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Functions of Heat Shock Proteins in Pathways of the Innate and Adaptive Immune System [BRIEF REVIEWS]

For more than 50 years, heat shock proteins (HSPs) have been studied for their role in protecting cells from elevated temperature and other forms of stress. More recently, several roles have been ascribed to HSPs in the immune system.

Via Gilbert Faure au nom de l'ASSIM
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Gilbert Faure au nom de l'ASSIM's curator insight, December 12, 4:13 AM
Abstract

For more than 50 years, heat shock proteins (HSPs) have been studied for their role in protecting cells from elevated temperature and other forms of stress. More recently, several roles have been ascribed to HSPs in the immune system. These include intracellular roles in Ag presentation and expression of innate receptors, as well as extracellular roles in tumor immunosurveillance and autoimmunity. Exogenously administered HSPs can elicit a variety of immune responses that have been used in immunotherapy of cancer, infectious diseases, and autoimmune disease.

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MicroRNA miR-320a and miR-140 inhibit mink enteritis virus infection by repression of its receptor, feline transferrin receptor

Mink enteritis virus (MEV) is one of the most important pathogens in the mink industry. Recent studies have shed light into the role of microRNAs (miRNAs), small noncoding RNAs of length ranging from 18¿23 nucleotides (nt), as critical modulators in the host-pathogen interaction networks. We previously showed that miRNA miR-181b can inhibit MEV replication by repression of viral non-structural protein 1 expression. Here, we report that two other miRNAs (miR-320a and miR-140) inhibit MEV entry into feline kidney (F81) cells by downregulating its receptor, transferrin receptor (TfR), by targeting the 3¿ untranslated region (UTR) of TfR mRNA, while being themselves upregulated.
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Building viruses that kill cancer cells: BeneVir gets $2M, waiting on $10M more

Building viruses that kill cancer cells: BeneVir gets $2M, waiting on $10M more | Host Cell & Pathogen Interactions | Scoop.it
Maryland startup BeneVir is developing immunotherapy viruses that rid the body of two types of tumor cells - those that cause cancer and the ones that make it recurrent.

Via Heather Swift
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How ZMapp antibodies bind to Ebola virus

How ZMapp antibodies bind to Ebola virus | Host Cell & Pathogen Interactions | Scoop.it
The structure of the antibodies in ZMapp bound to the Ebola virus glycoprotein reveal how they inhibit infection and how ZMapp might be improved.
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Scripps Research Institute Scientists Reveal Weak Spots in Ebola’s Defenses

Scripps Research Institute Scientists Reveal Weak Spots in Ebola’s Defenses | Host Cell & Pathogen Interactions | Scoop.it
News Release
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What Makes Ebola So Deadly? [VIDEO]

What Makes Ebola So Deadly? [VIDEO] | Host Cell & Pathogen Interactions | Scoop.it
The Ebola virus is able to kill its victim so quickly because of its effective warfare against a body's immune system.
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Alfonso Barrios Sanz's curator insight, November 11, 7:29 AM

The strain currently affecting is the most severe. This strain produces a strong hemorrhagic fever. Also it is a very contagious virus, so we have to take high security methods. 

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Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner

Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner | Host Cell & Pathogen Interactions | Scoop.it
From molecules to physiology
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First detailed picture of a cancer-related cell enzyme in action on a chromosome

First detailed picture of a cancer-related cell enzyme in action on a chromosome | Host Cell & Pathogen Interactions | Scoop.it

A landmark study published in the Oct. 30, print edition of the Nature provides new insight into the function of an enzyme related to the BRCA1 breast cancer protein. The study by a team at Penn State University is the first to produce a detailed working image of an enzyme in the Polycomb Repressive Complex 1 (PRC1) -- a group that regulates cell development and is associated with many types of cancer.


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Innate immunity summit

Innate immunity summit | Host Cell & Pathogen Interactions | Scoop.it
The Innate Immunity Summit, London, 10-12 Nov 2014 http://t.co/xS4azgK2yn

Via Gilbert Faure au nom de l'ASSIM
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Research shows viral DNA infects cells by changing from solid to fluid-like state

Research shows viral DNA infects cells by changing from solid to fluid-like state | Host Cell & Pathogen Interactions | Scoop.it
Many double-stranded DNA viruses infect cells by ejecting their genetic information into a host cell. But how does the usually rigid DNA packaged inside a virus' shell flow from the virus to the cell?
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GEN | News Highlights:With Cas9 Built-In, Mouse Is CRISPR-Ready

GEN | News Highlights:With Cas9 Built-In, Mouse Is CRISPR-Ready | Host Cell & Pathogen Interactions | Scoop.it
Broad Institute and MIT researchers engineer Cas9 animal models to study disease, inform drug discovery.
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Fesquet didier's curator insight, September 27, 11:06 AM

un autre outils pour customiser les genomes in vivo!