Scholar : ΦΩΝΗΤΙΚΕΣ ΧΟΡΔΕΣ - νέα αποτελέσματα

[PDF] Το μοιρολόι του Πόντου. Βιβλιογραφία & ηχογραφήσεις.

Γ Αμπερίδης - 2017

Page 1. ΤΕΙ ΗΠΕΙΡΟΥ ΣΧΟΛΗ ΚΑΛΛΙΤΕΧΝΙΚΩΝ ΣΠΟΥΔΩΝ ΤΜΗΜΑ ΛΑΪΚΗΣ ΚΑΙ ΠΑΡΑΔΟΣΙΑΚΗΣ
ΜΟΥΣΙΚΗΣ ΠΤΥΧΙΑΚΗ ΕΡΓΑΣΙΑ ΤΟ ΜΟΙΡΟΛΟΙ ΤΟΥ ΠΟΝΤΟΥ ΒΙΒΛΙΟΓΡΑΦΙΑ & ΗΧΟΓΡΑΦΗΣΕΙΣ
Φοιτητής: Αμπερίδης Γεώργιος Επιβλέπων: Γεώργιος Κοκκώνης …

[PDF] Ιορδάνης Τσομίδης: ένας «μάγος» της πενιάς. Το πορτραίτο του καλλιτέχνη μέσα από τα ταξίμια του.

ΙΣ Αγγελινάς - 2017

Page 1. ΤΕΙ ΗΠΕΙΡΟΥ ΣΧΟΛΗ ΜΟΥΣΙΚΗΣ ΤΕΧΝΟΛΟΓΙΑΣ ΤΜΗΜΑ ΛΑΙΚΗΣ ΚΑΙ
ΠΑΡΑΔΟΣΙΑΚΗΣ ΜΟΥΣΙΚΗΣ ΠΤΥΧΙΑΚΗ ΕΡΓΑΣΙΑ ΘΕΜΑ Ιορδάνης Τσομίδης: ένας
«μάγος» της πενιάς Το πορτραίτο του καλλιτέχνη μέσα από τα ταξίμια του …

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Αυτή η Ειδοποίηση του Μελετητή Google σας προσφέρεται από τη Google

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The key role of extracellular vesicles in the metastatic process

Publication date: Available online 24 November 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Hongyun Zhao, Abhinav Achreja, Elisabetta Iessi, Mariantonia Logozzi, Davide Mizzoni, Rossella Di Raimo, Deepak Nagrath, Stefano Fais
Extracellular vesicles (EVs), including exosomes, have a key role in the paracrine communication between organs and compartments. EVs shuttle virtually all types of biomolecules such as proteins, lipids, nucleic acids, metabolites and even pharmacological compounds. Their ability to transfer their biomolecular cargo into target cells enables EVs to play a key role in intercellular communication that can regulate cellular functions such as proliferation, apoptosis and migration. This has led to the emergence of EVs as a key player in tumor growth and metastasis through the formation of "tumor niches" in target organs. Recent data have also been shown that EVs may transform the microenvironment of primary tumors thus favoring the selection of cancer cells with a metastatic behavior. The release of EVs from resident non-malignant cells may contribute to the metastatic processes as well. However, cancer EVs may induce malignant transformation in resident mesenchymal stem cells, suggesting that the metastatic process is not exclusively due to circulating tumor cells. In this review, we outline and discuss evidence-based roles of EVs in actively regulating multiple steps of the metastatic process and how we can leverage EVs to impair metastasis.

Graphical abstract

http://ift.tt/2AAsM1d

Genetic host factors in Helicobacter pylori-induced carcinogenesis: Emerging new paradigms

Publication date: January 2018
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1869, Issue 1
Author(s): Michiel C. Mommersteeg, Jun Yu, Maikel P. Peppelenbosch, Gwenny M. Fuhler
Helicobacter Pylori is a gram negative rod shaped microaerophilic bacterium that colonizes the stomach of approximately half the world's population. Infection with c may cause chronic gastritis which via a quite well described process known as Correas cascade can progress through sequential development of atrophic gastritis, intestinal metaplasia and dysplasia to gastric cancer. H. pylori is currently the only bacterium that is classified as a class 1 carcinogen by the WHO, although the exact mechanisms by which this bacterium contributes to gastric carcinogenesis are still poorly understood. Only a minority of H. pylori-infected patients will eventually develop gastric cancer, suggesting that host factors may be important in determining the outcome of H. pylori infection. This is supported by a growing body of evidence suggesting that the host genetic background contributes to risk of H. pylori infection and gastric carcinogenesis. In particular single nucleotide polymorphisms in genes that influence bacterial handling via pattern recognition receptors appear to be involved, further strengthening the link between host risk factors, H. pylori incidence and cancer. Many of these genes influence cellular pathways leading to inflammatory signaling, inflammasome formation and autophagy. In this review we summarize known carcinogenic effects of H. pylori, and discuss recent findings that implicate host genetic pattern recognition pathways in the development of gastric cancer and their relation with H. pylori.



http://ift.tt/2ADUcDr

Long pentraxin 3: A novel multifaceted player in cancer

Publication date: January 2018
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1869, Issue 1
Author(s): Arianna Giacomini, Gaia Cristina Ghedini, Marco Presta, Roberto Ronca
Since its discovery in 1992, long pentraxin 3 (PTX3) has been characterized as soluble patter recognition receptor, a key player of the innate immunity arm with non-redundant functions in pathogen recognition and inflammatory responses. As a component of the extra-cellular matrix milieu, PTX3 has been implicated also in wound healing/tissue remodeling, cardiovascular diseases, fertility, and infectious diseases. Consequently, PTX3 levels in biological fluids have been proposed as a fluid-phase biomarker in different pathological conditions.In the last decade, experimental evidences have shown that PTX3 may exert a significant impact also on different aspects of cancer biology, including tumor onset, angiogenesis, metastatic dissemination and immune-modulation. However, it remains unclear whether PTX3 acts as a good cop or bad cop in cancer. In this review, we will summarize and discuss the scientific literature data focusing on the role of PTX3 in experimental and human tumors, including its putative translational implications.



http://ift.tt/2BwzsRN

Scholar : ΦΩΝΗΤΙΚΕΣ ΧΟΡΔΕΣ - νέα αποτελέσματα

[PDF] Το μοιρολόι του Πόντου. Βιβλιογραφία & ηχογραφήσεις.

Γ Αμπερίδης - 2017

Page 1. ΤΕΙ ΗΠΕΙΡΟΥ ΣΧΟΛΗ ΚΑΛΛΙΤΕΧΝΙΚΩΝ ΣΠΟΥΔΩΝ ΤΜΗΜΑ ΛΑΪΚΗΣ ΚΑΙ ΠΑΡΑΔΟΣΙΑΚΗΣ
ΜΟΥΣΙΚΗΣ ΠΤΥΧΙΑΚΗ ΕΡΓΑΣΙΑ ΤΟ ΜΟΙΡΟΛΟΙ ΤΟΥ ΠΟΝΤΟΥ ΒΙΒΛΙΟΓΡΑΦΙΑ & ΗΧΟΓΡΑΦΗΣΕΙΣ
Φοιτητής: Αμπερίδης Γεώργιος Επιβλέπων: Γεώργιος Κοκκώνης …

[PDF] Ιορδάνης Τσομίδης: ένας «μάγος» της πενιάς. Το πορτραίτο του καλλιτέχνη μέσα από τα ταξίμια του.

ΙΣ Αγγελινάς - 2017

Page 1. ΤΕΙ ΗΠΕΙΡΟΥ ΣΧΟΛΗ ΜΟΥΣΙΚΗΣ ΤΕΧΝΟΛΟΓΙΑΣ ΤΜΗΜΑ ΛΑΙΚΗΣ ΚΑΙ
ΠΑΡΑΔΟΣΙΑΚΗΣ ΜΟΥΣΙΚΗΣ ΠΤΥΧΙΑΚΗ ΕΡΓΑΣΙΑ ΘΕΜΑ Ιορδάνης Τσομίδης: ένας
«μάγος» της πενιάς Το πορτραίτο του καλλιτέχνη μέσα από τα ταξίμια του …

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Αυτή η Ειδοποίηση του Μελετητή Google σας προσφέρεται από τη Google

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Δημιουργία λίστας των ειδοποιήσεών μου

Cystic Fibrosis Transmembrane Conductance Regulator Attaches Tumor Suppressor PTEN to the Membrane and Promotes Anti Pseudomonas aeruginosa Immunity

Publication date: Available online 12 December 2017
Source:Immunity
Author(s): Sebastián A. Riquelme, Benjamin D. Hopkins, Andrew L. Wolfe, Emily DiMango, Kipyegon Kitur, Ramon Parsons, Alice Prince
The tumor suppressor PTEN controls cell proliferation by regulating phosphatidylinositol-3-kinase (PI3K) activity, but the participation of PTEN in host defense against bacterial infection is less well understood. Anti-inflammatory PI3K-Akt signaling is suppressed in patients with cystic fibrosis (CF), a disease characterized by hyper-inflammatory responses to airway infection. We found that Ptenl^−/− mice, which lack the NH2-amino terminal splice variant of PTEN, were unable to eradicate Pseudomonas aeruginosa from the airways and could not generate sufficient anti-inflammatory PI3K activity, similar to what is observed in CF. PTEN and the CF transmembrane conductance regulator (CFTR) interacted directly and this interaction was necessary to position PTEN at the membrane. CF patients under corrector-potentiator therapy, which enhances CFTR transport to the membrane, have increased PTEN amounts. These findings suggest that improved CFTR trafficking could enhance P. aeruginosa clearance from the CF airway by activating PTEN-mediated anti-bacterial responses and might represent a therapeutic strategy.

Graphical abstract

Teaser

Anti-inflammatory PI3K-Akt signaling is suppressed in patients with cystic fibrosis (CF), a disease characterized by hyper-inflammatory responses to airway infection. Riquelme et al. find that CFTR channel directly interacts with tumor suppressor PTEN, which regulates PI3K activity. CFTR helps position PTEN at the membrane to promote PTEN function and host immunity against Pseudomonas aeruginosa infection.


http://ift.tt/2kAzX2z

Roquin Suppresses the PI3K-mTOR Signaling Pathway to Inhibit T Helper Cell Differentiation and Conversion of Treg to Tfr Cells

Publication date: Available online 12 December 2017
Source:Immunity
Author(s): Katharina Essig, Desheng Hu, Joao C. Guimaraes, Dominik Alterauge, Stephanie Edelmann, Timsse Raj, Jan Kranich, Gesine Behrens, Alexander Heiseke, Stefan Floess, Juliane Klein, Andreas Maiser, Susan Marschall, Martin Hrabĕ de Angelis, Heinrich Leonhardt, Cornelis F. Calkhoven, Elfriede Noessner, Thomas Brocker, Jochen Huehn, Anne B. Krug, Mihaela Zavolan, Dirk Baumjohann, Vigo Heissmeyer
Roquin proteins preclude spontaneous T cell activation and aberrant differentiation of T follicular helper (Tfh) or T helper 17 (Th17) cells. Here we showed that deletion of Roquin-encoding alleles specifically in regulatory T (Treg) cells also caused the activation of conventional T cells. Roquin-deficient Treg cells downregulated CD25, acquired a follicular Treg (Tfr) cell phenotype, and suppressed germinal center reactions but could not protect from colitis. Roquin inhibited the PI3K-mTOR signaling pathway by upregulation of Pten through interfering with miR-17∼92 binding to an overlapping cis-element in the Pten 3′ UTR, and downregulated the Foxo1-specific E3 ubiquitin ligase Itch. Loss of Roquin enhanced Akt-mTOR signaling and protein synthesis, whereas inhibition of PI3K or mTOR in Roquin-deficient T cells corrected enhanced Tfh and Th17 or reduced iTreg cell differentiation. Thereby, Roquin-mediated control of PI3K-mTOR signaling prevents autoimmunity by restraining activation and differentiation of conventional T cells and specialization of Treg cells.

Graphical abstract

Teaser

Essig et al. show that spontaneous activation and aberrant differentiation of Roquin-deficient T cells involves cell-intrinsic causes in not only conventional T cells but also impaired Treg cell function. In both cell types, Roquin inhibits the PI3K-mTOR signaling pathway at several levels, thereby controlling protein biosynthesis and limiting differentiation toward Th17 and Tfh cells as well as preventing the conversion and functional specialization of Treg into Tfr cells.


http://ift.tt/2olrqpD

Oncogenic RAS Signaling Promotes Tumor Immunoresistance by Stabilizing PD-L1 mRNA

Publication date: Available online 12 December 2017
Source:Immunity
Author(s): Matthew A. Coelho, Sophie de Carné Trécesson, Sareena Rana, Davide Zecchin, Christopher Moore, Miriam Molina-Arcas, Philip East, Bradley Spencer-Dene, Emma Nye, Karin Barnouin, Ambrosius P. Snijders, Wi S. Lai, Perry J. Blackshear, Julian Downward
The immunosuppressive protein PD-L1 is upregulated in many cancers and contributes to evasion of the host immune system. The relative importance of the tumor microenvironment and cancer cell-intrinsic signaling in the regulation of PD-L1 expression remains unclear. We report that oncogenic RAS signaling can upregulate tumor cell PD-L1 expression through a mechanism involving increases in PD-L1 mRNA stability via modulation of the AU-rich element-binding protein tristetraprolin (TTP). TTP negatively regulates PD-L1 expression through AU-rich elements in the 3′ UTR of PD-L1 mRNA. MEK signaling downstream of RAS leads to phosphorylation and inhibition of TTP by the kinase MK2. In human lung and colorectal tumors, RAS pathway activation is associated with elevated PD-L1 expression. In vivo, restoration of TTP expression enhances anti-tumor immunity dependent on degradation of PD-L1 mRNA. We demonstrate that RAS can drive cell-intrinsic PD-L1 expression, thus presenting therapeutic opportunities to reverse the innately immunoresistant phenotype of RAS mutant cancers.

Graphical abstract

Teaser

Coelho et al. demonstrate a post-transcriptional mechanism whereby oncogenic RAS signaling increases PD-L1 expression. Mechanistically, PD-L1 mRNA is targeted by TTP through AU-rich elements in the 3′ UTR, making it unstable. Oncogenic RAS signaling reduces TTP activity and stabilizes the PD-L1 transcript. Restoring TTP activity reduces PD-L1 expression and enhances anti-tumor immunity.


http://ift.tt/2ol7iE0

White Adipose Tissue Is a Reservoir for Memory T Cells and Promotes Protective Memory Responses to Infection

Publication date: Available online 5 December 2017
Source:Immunity
Author(s): Seong-Ji Han, Arielle Glatman Zaretsky, Vinicius Andrade-Oliveira, Nicholas Collins, Amiran Dzutsev, Jahangheer Shaik, Denise Morais da Fonseca, Oliver J. Harrison, Samira Tamoutounour, Allyson L. Byrd, Margery Smelkinson, Nicolas Bouladoux, James B. Bliska, Jason M. Brenchley, Igor E. Brodsky, Yasmine Belkaid
White adipose tissue bridges body organs and plays a fundamental role in host metabolism. To what extent adipose tissue also contributes to immune surveillance and long-term protective defense remains largely unknown. Here, we have shown that at steady state, white adipose tissue contained abundant memory lymphocyte populations. After infection, white adipose tissue accumulated large numbers of pathogen-specific memory T cells, including tissue-resident cells. Memory T cells in white adipose tissue expressed a distinct metabolic profile, and white adipose tissue from previously infected mice was sufficient to protect uninfected mice from lethal pathogen challenge. Induction of recall responses within white adipose tissue was associated with the collapse of lipid metabolism in favor of antimicrobial responses. Our results suggest that white adipose tissue represents a memory T cell reservoir that provides potent and rapid effector memory responses, positioning this compartment as a potential major contributor to immunological memory.

Graphical abstract

Teaser

The role of adipose tissue in protective immunity is largely unknown. Han et al. reveal that white adipose tissue is a reservoir for memory T cells endowed with a distinct functional and metabolic profile. These memory T cells are able to protect against infection while inducing physiological remodeling of adipose tissue.


http://ift.tt/2kApfcv

Ablation of Transcription Factor IRF4 Promotes Transplant Acceptance by Driving Allogenic CD4+ T Cell Dysfunction

Publication date: Available online 5 December 2017
Source:Immunity
Author(s): Jie Wu, Hedong Zhang, Xiaomin Shi, Xiang Xiao, Yihui Fan, Laurie J. Minze, Jin Wang, Rafik M. Ghobrial, Jiahong Xia, Roger Sciammas, Xian C. Li, Wenhao Chen
CD4⁺ T cells orchestrate immune responses and destruction of allogeneic organ transplants, but how this process is regulated on a transcriptional level remains unclear. Here, we demonstrated that interferon regulatory factor 4 (IRF4) was a key transcriptional determinant controlling T cell responses during transplantation. IRF4 deletion in mice resulted in progressive establishment of CD4⁺ T cell dysfunction and long-term allograft survival. Mechanistically, IRF4 repressed PD-1, Helios, and other molecules associated with T cell dysfunction. In the absence of IRF4, chromatin accessibility and binding of Helios at PD-1 cis-regulatory elements were increased, resulting in enhanced PD-1 expression and CD4⁺ T cell dysfunction. The dysfunctional state of Irf4-deficient T cells was initially reversible by PD-1 ligand blockade, but it progressively developed into an irreversible state. Hence, IRF4 controls a core regulatory circuit of CD4⁺ T cell dysfunction, and targeting IRF4 represents a potential therapeutic strategy for achieving transplant acceptance.

Graphical abstract

Teaser

CD4⁺ T cells drive allogeneic organ transplant destruction, but how this is regulated transcriptionally remains unclear. Wu et al. report that IRF4 deletion in T cells leads to the establishment of T cell dysfunction and long-term allograft survival. Therefore, targeting IRF4 represents a therapeutic opportunity for achieving transplant acceptance.


http://ift.tt/2kAzrl9

Transcription Factor IRF4 Promotes CD8+ T Cell Exhaustion and Limits the Development of Memory-like T Cells during Chronic Infection

Publication date: Available online 12 December 2017
Source:Immunity
Author(s): Kevin Man, Sarah S. Gabriel, Yang Liao, Renee Gloury, Simon Preston, Darren C. Henstridge, Marc Pellegrini, Dietmar Zehn, Friederike Berberich-Siebelt, Mark A. Febbraio, Wei Shi, Axel Kallies
During chronic stimulation, CD8⁺ T cells acquire an exhausted phenotype characterized by expression of inhibitory receptors, down-modulation of effector function, and metabolic impairments. T cell exhaustion protects from excessive immunopathology but limits clearance of virus-infected or tumor cells. We transcriptionally profiled antigen-specific T cells from mice infected lymphocytic choriomeningitis virus strains that cause acute or chronic disease. T cell exhaustion during chronic infection was driven by high amounts of T cell receptor (TCR)-induced transcription factors IRF4, BATF, and NFATc1. These regulators promoted expression of inhibitory receptors, including PD-1, and mediated impaired cellular metabolism. Furthermore, they repressed the expression of TCF1, a transcription factor required for memory T cell differentiation. Reducing IRF4 expression restored the functional and metabolic properties of antigen-specific T cells and promoted memory-like T cell development. These findings indicate that IRF4 functions as a central node in a TCR-responsive transcriptional circuit that establishes and sustains T cell exhaustion during chronic infection.

Graphical abstract

Teaser

During chronic stimulation, CD8⁺ T cells acquire an exhausted phenotype characterized by expression of inhibitory receptors, loss of effector function, and metabolic impairments. Man et al. have identified a transcriptional module consisting of the TCR-induced transcription factors IRF4, BATF, and NFATc1 that drives T cell exhaustion and impairs memory T cell development.


http://ift.tt/2kzw2TV

High-Dimensional Phenotypic Mapping of Human Dendritic Cells Reveals Interindividual Variation and Tissue Specialization

Publication date: Available online 5 December 2017
Source:Immunity
Author(s): Marcela Alcántara-Hernández, Rebecca Leylek, Lisa E. Wagar, Edgar G. Engleman, Tibor Keler, M. Peter Marinkovich, Mark M. Davis, Garry P. Nolan, Juliana Idoyaga
Given the limited efficacy of clinical approaches that rely on ex vivo generated dendritic cells (DCs), it is imperative to design strategies that harness specialized DC subsets in situ. This requires delineating the expression of surface markers by DC subsets among individuals and tissues. Here, we performed a multiparametric phenotypic characterization and unbiased analysis of human DC subsets in blood, tonsil, spleen, and skin. We uncovered previously unreported phenotypic heterogeneity of human cDC2s among individuals, including variable expression of functional receptors such as CD172a. We found marked differences in DC subsets localized in blood and lymphoid tissues versus skin, and a striking absence of the newly discovered Axl⁺ DCs in the skin. Finally, we evaluated the capacity of anti-receptor monoclonal antibodies to deliver vaccine components to skin DC subsets. These results offer a promising path for developing DC subset-specific immunotherapies that cannot be provided by transcriptomic analysis alone.

Graphical abstract

Teaser

Dendritic cells (DCs) are potent initiators of immune responses; however, human DC subsets have yet to be successfully harnessed for immunotherapies. By combining CyTOF and unbiased analysis, Alcántara-Hernández et al. profile the heterogeneity of human DC subsets among individuals and tissues, providing comprehensive insights for the development of DC-based therapeutics.


http://ift.tt/2kyuSba

HIV Envelope Glycoform Heterogeneity and Localized Diversity Govern the Initiation and Maturation of a V2 Apex Broadly Neutralizing Antibody Lineage

Publication date: 21 November 2017
Source:Immunity, Volume 47, Issue 5
Author(s): Elise Landais, Ben Murrell, Bryan Briney, Sasha Murrell, Kimmo Rantalainen, Zachary T. Berndsen, Alejandra Ramos, Lalinda Wickramasinghe, Melissa Laird Smith, Kemal Eren, Natalia de Val, Mengyu Wu, Audrey Cappelletti, Jeffrey Umotoy, Yolanda Lie, Terri Wrin, Paul Algate, Po-Ying Chan-Hui, Etienne Karita, Andrew B. Ward, Ian A. Wilson, Dennis R. Burton, Davey Smith, Sergei L. Kosakovsky Pond, Pascal Poignard
Understanding how broadly neutralizing antibodies (bnAbs) to HIV envelope (Env) develop during natural infection can help guide the rational design of an HIV vaccine. Here, we described a bnAb lineage targeting the Env V2 apex and the Ab-Env co-evolution that led to development of neutralization breadth. The lineage Abs bore an anionic heavy chain complementarity-determining region 3 (CDRH3) of 25 amino acids, among the shortest known for this class of Abs, and achieved breadth with only 10% nucleotide somatic hypermutation and no insertions or deletions. The data suggested a role for Env glycoform heterogeneity in the activation of the lineage germline B cell. Finally, we showed that localized diversity at key V2 epitope residues drove bnAb maturation toward breadth, mirroring the Env evolution pattern described for another donor who developed V2-apex targeting bnAbs. Overall, these findings suggest potential strategies for vaccine approaches based on germline-targeting and serial immunogen design.

Graphical abstract

Teaser

Understanding the molecular basis of HIV Env-specific broadly neutralizing antibodies (bnAbs) development is key for vaccine design. Landais et al. find that glycan heterogeneity played a role in the activation of V2 apex PCT64 bnAbs precursor and that viral evolution was similar to CAP256, another donor with V2 apex bnAbs.


http://ift.tt/2kz01ve

Natural Parasite Exposure Induces Protective Human Anti-Malarial Antibodies

Publication date: Available online 29 November 2017
Source:Immunity
Author(s): Gianna Triller, Stephen W. Scally, Giulia Costa, Maria Pissarev, Cornelia Kreschel, Alexandre Bosch, Eric Marois, Brandon K. Sack, Rajagopal Murugan, Ahmed M. Salman, Chris J. Janse, Shahid M. Khan, Stefan H.I. Kappe, Ayola A. Adegnika, Benjamin Mordmüller, Elena A. Levashina, Jean-Philippe Julien, Hedda Wardemann
Antibodies against the NANP repeat of circumsporozoite protein (CSP), the major surface antigen of Plasmodium falciparum (Pf) sporozoites, can protect from malaria in animal models but are difficult to induce in humans. Here we cloned and characterized rare affinity-matured human NANP-reactive memory B cell antibodies elicited by natural Pf exposure that potently inhibited parasite transmission and development in vivo. We unveiled the molecular details of antibody binding to two distinct protective epitopes within the NANP repeat. NANP repeat recognition was largely mediated by germline encoded and immunoglobulin (Ig) heavy-chain complementarity determining region 3 (HCDR3) residues, whereas affinity maturation contributed predominantly to stabilizing the antigen-binding site conformation. Combined, our findings illustrate the power of exploring human anti-CSP antibody responses to develop tools for malaria control in the mammalian and the mosquito vector and provide a molecular basis for the structure-based design of next-generation CSP malaria vaccines.

Graphical abstract

Teaser

CSP is the target of protective antibodies against the malaria parasite Plasmodium falciparum (Pf). Here, Triller and Scally et al. identified potent Pf-inhibitory human anti-CSP memory B cell antibodies induced by natural exposure and unveiled the molecular details of antigen binding to two protective CSP repeat epitopes.


http://ift.tt/2kAEBOi

The Pore-Forming Protein Gasdermin D Regulates Interleukin-1 Secretion from Living Macrophages

Publication date: Available online 28 November 2017
Source:Immunity
Author(s): Charles L. Evavold, Jianbin Ruan, Yunhao Tan, Shiyu Xia, Hao Wu, Jonathan C. Kagan
The interleukin-1 (IL-1) family cytokines are cytosolic proteins that exhibit inflammatory activity upon release into the extracellular space. These factors are released following various cell death processes, with pyroptosis being a common mechanism. Recently, it was recognized that phagocytes can achieve a state of hyperactivation, which is defined by their ability to secrete IL-1 while retaining viability, yet it is unclear how IL-1 can be secreted from living cells. Herein, we report that the pyroptosis regulator gasdermin D (GSDMD) was necessary for IL-1β secretion from living macrophages that have been exposed to inflammasome activators, such as bacteria and their products or host-derived oxidized lipids. Cell- and liposome-based assays demonstrated that GSDMD pores were required for IL-1β transport across an intact lipid bilayer. These findings identify a non-pyroptotic function for GSDMD, and raise the possibility that GSDMD pores represent conduits for the secretion of cytosolic cytokines under conditions of cell hyperactivation.

Graphical abstract

Teaser

Inflammasomes elicit pyroptosis or cell hyperactivation, with the latter defined as living cells that release IL-1. Evavold et al report that the pore-forming protein gasdermin D regulates IL-1 release from hyperactive macrophages. Cell- and liposome-based assays revealed that gasdermin D pores permit IL-1 passage across intact lipid bilayers.


http://ift.tt/2kApe8r

The TCR Takes Some Immune Responsibility

Publication date: 21 November 2017
Source:Immunity, Volume 47, Issue 5
Author(s): Ashley A. Viehmann Milam, Paul M. Allen
In this issue of Immunity, Van Braeckel-Budimir et al. (2017) reveal that the pathogenic response of mice to a Plasmodium berghei infection is dominated by a Vβ8.1 T cell response. Mice lacking Vβ8.1 T cells fail to mount a pathogenic response, thus showing that the TCR locus can be an Immune response (Ir) gene.

Teaser

In this issue of Immunity, Van Braeckel-Budimir et al. (2017) reveal that the pathogenic response of mice to a Plasmodium berghei infection is dominated by a Vβ8.1 T cell response. Mice lacking Vβ8.1 T cells fail to mount a pathogenic response, thus showing that the TCR locus can be an Immune response (Ir) gene.


http://ift.tt/2om4BSC

A Sweet Solution: Glycolysis-Dependent Treg Cell Migration

Publication date: 21 November 2017
Source:Immunity, Volume 47, Issue 5
Author(s): Ronen Alon
mTORC2 is a metabolic regulatory complex activated by PI3K. In this issue of Immunity, Kishore et al. (2017) demonstrate a specialized role for this complex in the migration of regulatory T (Treg) cells to sites of inflammation rather than their differentiation and survival.

Teaser

mTORC2 is a metabolic regulatory complex activated by PI3K. In this issue of Immunity, Kishore et al. (2017) demonstrate a specialized role for this complex in the migration of regulatory T (Treg) cells to sites of inflammation rather than their differentiation and survival.


http://ift.tt/2CCVArk

TGF-β Gives an Air of Exclusivity to Alveolar Macrophages

Publication date: 21 November 2017
Source:Immunity, Volume 47, Issue 5
Author(s): Bart N. Lambrecht
Tissue-resident macrophages shape the development and homeostasis of the organs that they colonize. Yu et al. (2017) demonstrate that, unique to the lung, the instructive cytokine TGF-β collaborates with GM-CSF to induce the master transcription factor PPARγ to drive alveolar macrophage differentiation and maintenance early in life.

Teaser

Tissue-resident macrophages shape the development and homeostasis of the organs that they colonize. Yu et al. (2017) demonstrate that, unique to the lung, the instructive cytokine TGF-β collaborates with GM-CSF to induce the master transcription factor PPARγ to drive alveolar macrophage differentiation and maintenance early in life.


http://ift.tt/2ol66R2

The Silent Undertakers: Macrophages Programmed for Efferocytosis

Publication date: 21 November 2017
Source:Immunity, Volume 47, Issue 5
Author(s): Judith E. Allen, Dominik Rückerl
Two recent Immunity papers provide new insight into efferocytosis by tissue-resident macrophages. Baratin et al. (2017) identify a resident macrophage population in the T cell zone of lymph nodes responsible for the silent uptake of vast numbers of apoptotic cells. Roberts et al. (2017) find that resident macrophages can be programmed by local tissue signals not to respond to the nucleic acid of apoptotic cells.

Teaser

Two recent Immunity papers provide new insight into efferocytosis by tissue-resident macrophages. Baratin et al. (2017) identify a resident macrophage population in the T cell zone of lymph nodes responsible for the silent uptake of vast numbers of apoptotic cells. Roberts et al. (2017) find that resident macrophages can be programmed by local tissue signals not to respond to the nucleic acid of apoptotic cells.


http://ift.tt/2CDvCny

The Skinny: Pancreatic ILC2s Promote Insulin Secretion

Publication date: 21 November 2017
Source:Immunity, Volume 47, Issue 5
Author(s): Kelly M. Cautivo, Ari B. Molofsky
Regulation of pancreatic insulin production is pivotal in the pathophysiology and treatment of diabetes. In this issue of Immunity, Dalmas et al. (2017) describe a type 2 immune circuit where pancreatic interleukin-33 (IL-33) promotes insulin secretion via the activity of islet-associated group 2 innate lymphoid cells (ILC2s).

Teaser

Regulation of pancreatic insulin production is pivotal in the pathophysiology and treatment of diabetes. In this issue of Immunity, Dalmas et al. (2017) describe a type 2 immune circuit where pancreatic interleukin-33 (IL-33) promotes insulin secretion via the activity of islet-associated group 2 innate lymphoid cells (ILC2s).


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