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Curated by Gilbert C FAURE

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Scooped by Gilbert C FAURE

October 15, 2015 2:18 PM

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From journals.plos.org - October 13, 2015 5:00 PM

Gilbert C FAURE's insight:

Abstract

Ex vivo generated monocyte-derived dendritic cell (moDC)-vaccines have long been touted as promising immunotherapeutic agents for cancer treatment, although the response rate generally remains low. The reasons for this are still unclear and confounded by the diversity in manufacturing protocols that may affect moDC function. Preclinical studies have shown that the stimulatory function of dendritic cells can be improved by engaging invariant NKT cells in vivo through the presentation of the glycolipid alpha-galactosylceramide via CD1d. However, expression of CD1d on moDC has been shown to be negatively correlated with expression of CD1a, which in turn has been suggested to be a surrogate marker for IL-12 secreting type-1 polarized moDC, the preferred functional characteristics for cancer vaccines. Here we challenge this notion by showing that plasma-derived lipids drive functional levels of CD1d expression, while CD1a expression can vary considerably in these cells without being correlated with a loss of polarization or immunogenicity.

Gilbert C FAURE's curator insight, October 19, 2015 5:21 AM

Abstract

Krishan Maggon 's curator insight, October 19, 2015 2:16 PM

Citation: Mester B, Bauer E, Wood CE, Hermans IF, Gasser O (2015) Expression of CD1a and Type-1 Polarization Are Dissociated in Human Monocyte-Derived Dendritic Cells. PLoS ONE 10(10): e0140432. doi:10.1371/journal.pone.0140432

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October 14, 2015 2:06 PM

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Permissive and protective roles for neutrophils in leishmaniasis - Carlsen - 2015 - Clinical & Experimental Immunology - Wiley Online Library | Immunology | Scoop.it

From onlinelibrary.wiley.com - October 14, 2015 12:44 PM

Gilbert C FAURE's insight:

Summary

Leishmania parasites are the causative agents of leishmaniasis, a neglected tropical disease that causes substantial morbidity and considerable mortality in many developing areas of the world. Recent estimates suggest that roughly 10 million people suffer from cutaneous leishmaniasis (CL), and approximately 76 000 are afflicted with visceral leishmaniasis (VL), which is universally fatal without treatment. Efforts to develop therapeutics and vaccines have been greatly hampered by an incomplete understanding of the parasite's biology and a lack of clear protective correlates that must be met in order to achieve immunity. Although parasites grow and divide preferentially in macrophages, a number of other cell types interact with and internalize Leishmania parasites, including monocytes, dendritic cells and neutrophils. Neutrophils appear to be especially important shortly after parasites are introduced into the skin, and may serve a dual protective and permissive role during the establishment of infection. Curiously, neutrophil recruitment to the site of infection appears to continue into the chronic phase of disease, which may persist for many years. The immunological impact of these cells during chronic leishmaniasis is unclear at this time. In this review we discuss the ways in which neutrophils have been observed to prevent and promote the establishment of infection, examine the role of anti-neutrophil antibodies in mouse models of leishmaniasis and consider recent findings that neutrophils may play a previously unrecognized role in influencing chronic parasite persistence.

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Scooped by Gilbert C FAURE

October 14, 2015 10:05 AM

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From intimm.oxfordjournals.org - October 13, 2015 11:20 PM

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Scooped by Gilbert C FAURE

October 13, 2015 5:11 AM

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From www.nature.com - October 12, 2015 4:59 AM

Gilbert C FAURE's insight:

Understanding of natural killer (NK) cell development in human is incomplete partly because of limited access to appropriate human tissues. We have developed a cytokine-enhanced humanized mouse model with greatly improved reconstitution and function of human NK cells. Here we report the presence of a cell population in the bone marrow of the cytokine-treated humanized mice that express both NK cell marker CD56 and myeloid markers such as CD36 and CD33. The CD56+CD33+CD36+ cells are also found in human cord blood, fetal and adult bone marrow. Although the CD56+CD33+CD36+ cells do not express the common NK cell functional receptors and exhibit little cytotoxic and cytokine-producing activities, they readily differentiate into mature NK cells by acquiring expression of NK cell receptors and losing expression of the myeloid markers. Further studies show that CD33+CD36+ myeloid NK precursors are derived from granulo-myelomonocytic progenitors. These results delineate the pathway of human NK cell differentiation from myeloid progenitors in the bone marrow and suggest the utility of humanized mice for studying human hematopoiesis.

Krishan Maggon 's curator insight, October 13, 2015 5:21 AM

Article | OPEN

Delineation of Natural Killer Cell Differentiation from Myeloid Progenitors in HumanQingfeng Chen, Weijian Ye, Wei Jian Tan, Kylie Su Mei Yong, Min Liu, Shu Qi Tan, Eva Loh, Kenneth TE Chang, Thiam Chye Tan, Peter R. Preiser & Jianzhu Chen

Scientific Reports 5, Article number: 15118 (2015)doi:10.1038/srep15118Haematopoiesis | NK cells

Received:01 July 2015Accepted:16 September 2015Published online:12 October 2015

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October 12, 2015 5:14 AM

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From www.pisa2015.org - October 8, 2015 10:06 AM

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Scooped by Gilbert C FAURE

October 11, 2015 12:38 PM

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From www.biorxiv.org - October 9, 2015 12:49 AM

Gilbert C FAURE's insight:

Motivation The T cell receptors are expressed as millions of different rearrangements. Amplified as a complex mixture of PCR products, they can be sequenced directly on next-generation instruments without the need for cloning. This method is increasingly used to characterize, quantify and study these highly diverse receptors. Results We present here clonotypeR, a software package to identify and analyze antigen receptors from high-throughput sequence libraries. ClonotypeR is designed to process, organize and analyze very large numbers of sequences, in the order of millions, typically produced by Roche 454 or Illumina instruments, and is made of two parts. The first contains shell scripts and reference segment sequences to produce a data file where each line represents a the detection of a clonotype in a sequence read. The second part is a R module available from Bioconductor, to load and filter the data, and prepare clonotype abundance tables ready for analysis with third-party tools for differential representation analysis, sample clustering, etc. To analyze clonotype data at the nucleotide level, we introduce unique clonotype identifiers based on those developed by Yassai et al. (2009), that we corrected to avoid identifier collisions. Availability http://clonotyper.branchable.com (CC0 license).

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Scooped by Gilbert C FAURE

October 10, 2015 4:32 PM

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From www.nature.com - October 9, 2015 3:20 AM

Gilbert C FAURE's insight:

Phosphatase CD45 regulates the activation of lymphocytes by controlling the level of receptor and signal molecule phosphorylation. However, it remains unknown which molecules mediate the phosphatase activity of CD45. A candidate for such a molecule is a small transmembrane adapter protein called lymphocyte phosphatase-associated phosphoprotein (LPAP). LPAP forms a supramolecular complex that consists of not only CD45 molecule but also CD4 and Lck kinase. The function of LPAP has not been defined clearly. In our study, we determined the pattern of LPAP expression in various cell types and characterized its proteoforms using new monoclonal antibodies generated against the intracellular portion of the protein. We show that LPAP is a pan-lymphocyte marker, and its expression in cells correlates with the expression of CD45. The majority of T, B and NK cells express high levels of LPAP, whereas monocytes, granulocytes, monocyte-derived dendritic cells, platelets and red blood cells are negative for LPAP. Using one- and two-dimensional protein gel electrophoresis, we demonstrate that LPAP has at least four sites of phosphorylation. The resting cells express at least six different LPAP phosphoforms representing mono-, di- and tri-phosphorylated LPAP. T and B cells differ in the distribution of the protein between phosphoforms. The activation of lymphocytes with PMA reduces the diversity of phosphorylated forms. Our experiments on Lck-deficient Jurkat cells show that Lck kinase is not involved in LPAP phosphorylation. Thus, LPAP is a dynamically phosphorylated protein, the function of which can be understood, when all phosphosites and kinases involved in its phosphorylation will be identified.

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Rescooped by Gilbert C FAURE from Biotech Pharma Innovation in Immuno-Oncology & beyond. Cancer - Immunology - Immunotherapy.

October 9, 2015 1:28 PM

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From www.nature.com - October 8, 2015 8:00 PM

Gilbert C FAURE's insight:

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Scooped by Gilbert C FAURE

October 8, 2015 3:17 PM

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From journals.plos.org - October 7, 2015 5:00 PM

Gilbert C FAURE's insight:

ADCC

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Scooped by Gilbert C FAURE

October 6, 2015 4:00 PM

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From www.ncbi.nlm.nih.gov - October 3, 2015 5:11 PM

Gilbert C FAURE's insight:

We have characterized CD8+ T cells from a patient with Good syndrome that presented with CD8+T-cell large granular lymphocytic leukemia (LGL). Characterization of peripheral blood CD8+ T cells revealed that majority of CD8+ T cells were terminally differentiated effector memory phenotype (TEMRA; CD8+CCR7-CD45RA+), and were PD-1high (CD279), ICOSlow (CD278), and granzymehigh. Almost all CD8+ T cells were IFN-γ+. CD8 Treg (CD8+CD183+CCR7+CD45RA-) were decreased. TEMRA phenotype along with CD279high, demonstrates that these are exhausted CD8+ T cells. This phenotype along with CD278low may also explain severe T cell functional deficiency in our patient.

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Suggested by Société Francaise d'Immunologie

October 6, 2015 3:17 PM

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From www.jimmunol.org - October 2, 2015 4:01 PM

Gilbert C FAURE's insight:

Regulatory T (Treg) cells have a critical role in the control of immunity, and their diverse subpopulations may allow adaptation to different types of immune responses. In this study, we analyzed human Treg cell subpopulations in the peripheral blood by performing genome-wide expression profiling of 40 Treg cell subsets from healthy donors. We found that the human peripheral blood Treg cell population is comprised of five major genomic subgroups, represented by 16 tractable subsets with a particular cell surface phenotype. These subsets possess a range of suppressive function and cytokine secretion and can exert a genomic footprint on target effector T (Teff) cells. Correlation analysis of variability in gene expression in the subsets identified several cell surface molecules associated with Treg suppressive function, and pharmacological interrogation revealed a set of genes having causative effect. The five genomic subgroups of Treg cells imposed a preserved pattern of gene expression on Teff cells, with a varying degree of genes being suppressed or induced. Notably, there was a cluster of genes induced by Treg cells that bolstered an autoinhibitory effect in Teff cells, and this induction appears to be governed by a different set of genes than ones involved in counteracting Teff activation. Our work shows an example of exploiting the diversity within human Treg cell subpopulations to dissect Treg cell biology.

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Scooped by Gilbert C FAURE

October 5, 2015 10:15 AM

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From journals.plos.org - October 2, 2015 5:00 PM

Gilbert C FAURE's insight:

Abstract

Neutrophils release fibrous traps of DNA, histones, and granule proteins known as neutrophil extracellular traps (NETs), which contribute to microbicidal killing and have been implicated in autoimmunity. The role of NET formation in the host response to nonbacterial pathogens is not well-understood. In this study, we investigated the release of NETs by human neutrophils upon their interaction with Trypanosoma cruzi (Y strain) parasites. Our results showed that human neutrophils stimulated by T. cruzi generate NETs composed of DNA, histones, and elastase. The release occurred in a dose-, time-, and reactive oxygen species-dependent manner to decrease trypomastigote and increase amastigote numbers of the parasites without affecting their viability. NET release was decreased upon blocking with antibodies against Toll-like receptors 2 and 4. In addition, living parasites were not mandatory in the release of NETs induced by T. cruzi, as the same results were obtained when molecules from its soluble extract were tested. Our results increase the understanding of the stimulation of NETs by parasites, particularly T. cruzi. We suggest that contact of T. cruzi with NETs during Chagas’s disease can limit infection by affecting the infectivity/pathogenicity of the parasite.

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Scooped by Gilbert C FAURE

October 4, 2015 3:02 PM

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From www.researchandmarkets.com - October 4, 2015 7:48 AM

Gilbert C FAURE's insight:

...... of an effective immune response to invading pathogens

As B and T lymphocytes are characterized by the expression of antigen receptors that specifically recognize determinants expressed on pathogens, this volume discusses how antigen receptors are synthesized in B and T lymphocytes.

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Scooped by Gilbert C FAURE

October 15, 2015 5:17 AM

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From medicalxpress.com - October 15, 2015 5:17 AM

Gilbert C FAURE's insight:

what I am saying to students in the lymph node course!

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Scooped by Gilbert C FAURE

October 14, 2015 10:06 AM

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From www.ncbi.nlm.nih.gov - October 13, 2015 2:38 PM

Gilbert C FAURE's insight:

Abstract

Systems-level analysis of biological processes strives to comprehensively and quantitatively evaluate the interactions between the relevant molecular components over time, thereby enabling development of models that can be employed to ultimately predict behavior. Rapid development in measurement technologies (omics), when combined with the accessible nature of the cellular constituents themselves, is allowing the field of innate immunity to take significant strides toward this lofty goal. In this review, we survey exciting results derived from systems biology analyses of the immune system, ranging from gene regulatory networks to influenza pathogenesis and systems vaccinology.

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Scooped by Gilbert C FAURE

October 13, 2015 2:59 PM

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From www.ncbi.nlm.nih.gov - October 4, 2015 6:09 AM

Gilbert C FAURE's insight:

Abstract

Serine protease inhibitor, represented by serpin, plays an important inhibitory role on proteases involved in the immune responses. To clarify the immune characterizations of serpin, a novel serpin (Lvserpin3) encoding for 410 amino acids with a 23-amino acid signal peptide and a serpin domain was identified from the Pacific white shrimp Litopenaeus vannamei......

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Scooped by Gilbert C FAURE

October 12, 2015 1:08 PM

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From atvb.ahajournals.org - September 28, 2015 2:40 PM

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Scooped by Gilbert C FAURE

October 12, 2015 5:11 AM

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The kinases NDR1/2 act downstream of the Hippo homolog MST1 to mediate both egress of thymocytes from the thymus and lymphocyte motility | Immunology | Scoop.it

From stke.sciencemag.org - October 11, 2015 7:10 AM

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Scooped by Gilbert C FAURE

October 11, 2015 12:32 PM

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From www.nature.com - October 9, 2015 8:01 AM

Gilbert C FAURE's insight:

Bcl2 family proteins control mitochondrial apoptosis and its members exert critical cell type and differentiation stage-specific functions, acting as barriers against autoimmunity or transformation. Anti-apoptoticBcl2a1/Bfl1/A1 is frequently deregulated in different types of blood cancers in humans but its physiological role is poorly understood as quadruplication of the Bcl2a1 gene locus in mice hampers conventional gene targeting strategies. Transgenic overexpression of A1, deletion of the A1-a paralogue or constitutive knockdown in the hematopoietic compartment of mice by RNAi suggested rate-limiting roles in lymphocyte development, granulopoiesis and mast cell activation. Here we report on the consequences of conditional knockdown of A1 protein expression using a reverse transactivator (rtTA)-driven approach that highlights a critical role for this Bcl2 family member in the maintenance of mature B-cell homeostasis. Furthermore, we define the A1/Bim (Bcl-2 interacting mediator of cell death) axis as a target of key kinases mediating B-cell receptor (BCR)-dependent survival signals, such as, spleen tyrosine kinase (Syk) and Brutons tyrosine kinase (Btk). As such, A1 represents a putative target for the treatment of B-cell-related pathologies depending on hyperactivation of BCR-emanating survival signals and loss of A1 expression accounts, in part, for the pro-apoptotic effects of Syk- or Btk inhibitors that rely on the ‘BH3-only’ protein Bim for cell killing.

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Scooped by Gilbert C FAURE

October 9, 2015 1:42 PM

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From www.scoop.it - October 9, 2015 12:48 AM

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Scooped by Gilbert C FAURE

October 9, 2015 3:44 AM

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From www.eurekalert.org - October 6, 2015 11:51 AM

Gilbert C FAURE's insight:

Sialic acid protects from antibody-induced cell killing

A team of researchers headed by Professor Jan Lünemann from the Institute of Experimental Immunology at the University of Zurich has now discovered that a particular sugar structure in the antibody plays a key role in the complement-dependent destruction of the body's own tissue. Antibodies consist of protein and coupled sugar groups. Earlier studies revealed that antibodies with the sugar structure sialic acid are detectable more rarely in patients suffering from autoimmune diseases than in healthy people.

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Scooped by Gilbert C FAURE

October 8, 2015 2:47 PM

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From nar.oxfordjournals.org - October 8, 2015 10:55 AM

Gilbert C FAURE's insight:

Here we present LymAnalzyer, a software package that significantly improves the completeness and accuracy of TCR/IG profiling from deep sequence data and includes procedures to identify novel alleles of gene segments. On real and simulated data sets LymAnalyzer produces highly accurate and complete results

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Scooped by Gilbert C FAURE

October 6, 2015 3:19 PM

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From www.research-in-germany.org - October 3, 2015 5:01 PM

Gilbert C FAURE's insight:

Percy Knolle and his team have now managed to identify a marker for killer cells for the first time. Their findings have been published in the journal Nature Communications. The scientists found a molecule – the CX3CR1 receptor – occurring only on the surface of these killer cells. They first demonstrated this in infection models with mice, and then verified their findings in a human patient study.

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Scooped by Gilbert C FAURE

October 6, 2015 9:09 AM

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From www.facebook.com - October 6, 2015 9:09 AM

Gilbert C FAURE's insight:

in a few days, enjoy

13-16 October

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Rescooped by Gilbert C FAURE from VIH et immunodéficiences acquises

October 5, 2015 6:05 AM

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From www.techtimes.com - October 2, 2015 5:42 PM

Gilbert C FAURE's insight:

Dendritic cells can capture and transfer retroviruses in vitro across synaptic cell-cell contacts to uninfected cells, a process called trans-infection. Whether trans-infection contributes to retroviral spread in vivo remains unknown. Here, we visualize how retroviruses disseminate in secondary lymphoid tissues of living mice. We demonstrate that murine leukemia virus (MLV) and human immunodeficiency virus (HIV) are first captured by sinus-lining macrophages. CD169/Siglec-1, an I-type lectin that recognizes gangliosides, captures the virus. MLV-laden macrophages then form long-lived synaptic contacts to trans-infect B-1 cells. Infected B-1 cells subsequently migrate into the lymph node to spread the infection through virological synapses. Robust infection in lymph nodes and spleen requires CD169, suggesting that a combination of fluid-based movement followed by CD169-dependent trans-infection can contribute to viral spread.

Société Francaise d'Immunologie's curator insight, October 5, 2015 6:02 AM

CD169 siglec

Immunology

Expression of CD1a and Type-1 Polarization Are Dissociated in Human Monocyte-Derived Dendritic Cells

Permissive and protective roles for neutrophils in leishmaniasis - Carlsen - 2015 - Clinical & Experimental Immunology - Wiley Online Library

Heterogeneity and diversity of group 3 innate lymphoid cells: new cells on the block

Delineation of Natural Killer Cell Differentiation from Myeloid Progenitors in ... - Nature.com

American Society for Investigative Pathology - PISA 2015.org - Meeting Program

clonotypeR--high throughput analysis of T cell antigen receptor sequences

Lymphocyte phosphatase-associated phosphoprotein proteoforms analyzed using ... - Nature.com

[gamma][delta] T cells in cancer

Importance of the Side Chain at Position 296 of Antibody Fc in Interactions with FcγRIIIa and Other Fcγ Receptors

Good syndrome presenting with CD8+ T-Cell large granular lymphocyte leukemia. - PubMed - NCBI

Diverse Gene Expression in Human Regulatory T Cell Subsets Uncovers Connection between Regulatory T Cell Genes and Suppressive Function [CLINICAL AND HUMAN IMMUNOLOGY]

Trypanosoma cruzi and Its Soluble Antigens Induce NET Release by Stimulating Toll-Like Receptors

Molecular Mechanisms That Orchestrate the Assembly of Antigen Receptor Loci, Vol 128. Advances in Immunology

Blood T cells are resistant to HIV's primary death pathway

Systems-level analysis of innate immunity. - PubMed - NCBI

Lvserpin3 is involved in shrimp innate immunity via the inhibition of bacterial proteases and proteases involved in prophenoloxidase system. - PubMed - NCBI

Deficiency of HIF1α in Antigen-Presenting Cells Aggravates Atherosclerosis and Type 1 T-Helper Cell Responses in Mice

The kinases NDR1/2 act downstream of the Hippo homolog MST1 to mediate both egress of thymocytes from the thymus and lymphocyte motility

Conditional knockdown of BCL2A1 reveals rate-limiting roles in BCR-dependent B ... - Nature.com

Antigen-specific NK cell memory in rhesus macaq...

Sugar governs how antibodies work in the immune system University of Zurich - EurekAlert (press release)

LymAnalyzer: a tool for comprehensive analysis of next generation sequencing data of T cell receptors and immunoglobulins

Cell marker enables prognosis about the course of infections - Research in Germany

Inmunocolombia2015

HIV Caught Spreading on Tape - Tech Times