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Immunity

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https://www.readbyqxmd.com/read/29150240/dichotomous-expression-of-tnf-superfamily-ligands-on-antigen-presenting-cells-controls-post-priming-anti-viral-cd4-t-cell-immunity
#1
Yu-Han Chang, Kuan Chung Wang, Kuan-Lun Chu, Derek L Clouthier, Anh T Tran, Miguel S Torres Perez, Angela C Zhou, Ali A Abdul-Sater, Tania H Watts
T cell antigen-presenting cell (APC) interactions early during chronic viral infection are crucial for determining viral set point and disease outcome, but how and when different APC subtypes contribute to these outcomes is unclear. The TNF receptor superfamily (TNFRSF) member GITR is important for CD4(+) T cell accumulation and control of chronic lymphocytic choriomeningitis virus (LCMV). We found that type I interferon (IFN-I) induced TNFSF ligands GITRL, 4-1BBL, OX40L, and CD70 predominantly on monocyte-derived APCs and CD80 and CD86 predominantly on classical dendritic cells (cDCs)...
November 13, 2017: Immunity
https://www.readbyqxmd.com/read/29150239/tissue-resident-macrophages-are-locally-programmed-for-silent-clearance-of-apoptotic-cells
#2
Allison W Roberts, Bettina L Lee, Jacques Deguine, Shinu John, Mark J Shlomchik, Gregory M Barton
Although apoptotic cells (ACs) contain nucleic acids that can be recognized by Toll-like receptors (TLRs), engulfment of ACs does not initiate inflammation in healthy organisms. Here we identified macrophage populations that continually engulf ACs in distinct tissues and found that these macrophages share characteristics compatible with immunologically silent clearance of ACs; such characteristics include high expression of AC recognition receptors, low expression of TLR9, and reduced TLR responsiveness to nucleic acids...
November 13, 2017: Immunity
https://www.readbyqxmd.com/read/29150241/targeting-interleukin-1%C3%AE-protects-from-aortic-aneurysms-induced-by-disrupted-transforming-growth-factor-%C3%AE-signaling
#3
Francesco Da Ros, Raimondo Carnevale, Giuseppe Cifelli, Dario Bizzotto, Manuel Casaburo, Marialuisa Perrotta, Lorenzo Carnevale, Iolanda Vinciguerra, Stefania Fardella, Roberta Iacobucci, Giorgio M Bressan, Paola Braghetta, Giuseppe Lembo, Daniela Carnevale
Aortic aneurysms are life-threatening conditions with effective treatments mainly limited to emergency surgery or trans-arterial endovascular stent grafts, thus calling for the identification of specific molecular targets. Genetic studies have highlighted controversial roles of transforming growth factor β (TGF-β) signaling in aneurysm development. Here, we report on aneurysms developing in adult mice after smooth muscle cell (SMC)-specific inactivation of Smad4, an intracellular transducer of TGF-β. The results revealed that Smad4 inhibition activated interleukin-1β (IL-1β) in SMCs...
November 10, 2017: Immunity
https://www.readbyqxmd.com/read/29150238/a-t-cell-receptor-locus-harbors-a-malaria-specific-immune-response-gene
#4
Natalija Van Braeckel-Budimir, Stephanie Gras, Kristin Ladell, Tracy M Josephs, Lecia Pewe, Stina L Urban, Kelly L Miners, Carine Farenc, David A Price, Jamie Rossjohn, John T Harty
Immune response (Ir) genes, originally proposed by Baruj Benacerraf to explain differential antigen-specific responses in animal models, have become synonymous with the major histocompatibility complex (MHC). We discovered a non-MHC-linked Ir gene in a T cell receptor (TCR) locus that was required for CD8(+) T cell responses to the Plasmodium berghei GAP5040-48 epitope in mice expressing the MHC class I allele H-2D(b). GAP5040-48-specific CD8(+) T cell responses emerged from a very large pool of naive Vβ8...
November 10, 2017: Immunity
https://www.readbyqxmd.com/read/29126798/cd4-t-cell-help-confers-a-cytotoxic-t-cell-effector-program-including-coinhibitory-receptor-downregulation-and-increased-tissue-invasiveness
#5
Tomasz Ahrends, Aldo Spanjaard, Bas Pilzecker, Nikolina Bąbała, Astrid Bovens, Yanling Xiao, Heinz Jacobs, Jannie Borst
CD4(+) T cells optimize the cytotoxic T cell (CTL) response in magnitude and quality, by unknown molecular mechanisms. We here present the transcriptomic changes in CTLs resulting from CD4(+) T cell help after anti-cancer vaccination or virus infection. The gene expression signatures revealed that CD4(+) T cell help during priming optimized CTLs in expression of cytotoxic effector molecules and many other functions that ensured efficacy of CTLs throughout their life cycle. Key features included downregulation of PD-1 and other coinhibitory receptors that impede CTL activity, and increased motility and migration capacities...
November 6, 2017: Immunity
https://www.readbyqxmd.com/read/29126797/the-cytokine-tgf-%C3%AE-promotes-the-development-and-homeostasis-of-alveolar-macrophages
#6
Xueyang Yu, Anne Buttgereit, Iva Lelios, Sebastian G Utz, Dilay Cansever, Burkhard Becher, Melanie Greter
Alveolar macrophages (AMs) derive from fetal liver monocytes, which colonize the lung during embryonic development and give rise to fully mature AMs perinatally. AM differentiation requires granulocyte macrophage colony-stimulating factor (GM-CSF), but whether additional factors are involved in AM regulation is not known. Here we report that AMs, in contrast to most other tissue macrophages, were also dependent on transforming growth factor-β receptor (TGF-βR) signaling. Conditional deletion of TGF-βR in mice at different time points halted the development and differentiation of AMs...
November 6, 2017: Immunity
https://www.readbyqxmd.com/read/29045907/reactive-neutrophil-responses-dependent-on-the-receptor-tyrosine-kinase-c-met-limit-cancer-immunotherapy
#7
Nicole Glodde, Tobias Bald, Debby van den Boorn-Konijnenberg, Kyohei Nakamura, Jake S O'Donnell, Sabrina Szczepanski, Maria Brandes, Sarah Eickhoff, Indrajit Das, Naveen Shridhar, Daniel Hinze, Meri Rogava, Tetje C van der Sluis, Janne J Ruotsalainen, Evelyn Gaffal, Jennifer Landsberg, Kerstin U Ludwig, Christoph Wilhelm, Monika Riek-Burchardt, Andreas J Müller, Christoffer Gebhardt, Richard A Scolyer, Georgina V Long, Viktor Janzen, Michele W L Teng, Wolfgang Kastenmüller, Massimiliano Mazzone, Mark J Smyth, Thomas Tüting, Michael Hölzel
Inhibitors of the receptor tyrosine kinase c-MET are currently used in the clinic to target oncogenic signaling in tumor cells. We found that concomitant c-MET inhibition promoted adoptive T cell transfer and checkpoint immunotherapies in murine cancer models by increasing effector T cell infiltration in tumors. This therapeutic effect was independent of tumor cell-intrinsic c-MET dependence. Mechanistically, c-MET inhibition impaired the reactive mobilization and recruitment of neutrophils into tumors and draining lymph nodes in response to cytotoxic immunotherapies...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045906/ctla-4-pd-1-memory-cd4-t-cells-critically-contribute-to-viral-persistence-in-antiretroviral-therapy-suppressed-siv-infected-rhesus-macaques
#8
Colleen S McGary, Claire Deleage, Justin Harper, Luca Micci, Susan P Ribeiro, Sara Paganini, Leticia Kuri-Cervantes, Clarisse Benne, Emily S Ryan, Robert Balderas, Sherrie Jean, Kirk Easley, Vincent Marconi, Guido Silvestri, Jacob D Estes, Rafick-Pierre Sekaly, Mirko Paiardini
Antiretroviral therapy (ART) suppresses viral replication in HIV-infected individuals but does not eliminate the reservoir of latently infected cells. Recent work identified PD-1(+) follicular helper T (Tfh) cells as an important cellular compartment for viral persistence. Here, using ART-treated, SIV-infected rhesus macaques, we show that CTLA-4(+)PD-1(-) memory CD4(+) T cells, which share phenotypic markers with regulatory T cells, were enriched in SIV DNA in blood, lymph nodes (LN), spleen, and gut, and contained replication-competent and infectious virus...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045905/transcriptional-reprogramming-during-effector-to-memory-transition-renders-cd4-t-cells-permissive-for-latent-hiv-1-infection
#9
Liang Shan, Kai Deng, Hongbo Gao, Sifei Xing, Adam A Capoferri, Christine M Durand, S Alireza Rabi, Gregory M Laird, Michelle Kim, Nina N Hosmane, Hung-Chih Yang, Hao Zhang, Joseph B Margolick, Linghua Li, Weiping Cai, Ruian Ke, Richard A Flavell, Janet D Siliciano, Robert F Siliciano
The latent reservoir for HIV-1 in resting memory CD4(+) T cells is the major barrier to curing HIV-1 infection. Studies of HIV-1 latency have focused on regulation of viral gene expression in cells in which latent infection is established. However, it remains unclear how infection initially becomes latent. Here we described a unique set of properties of CD4(+) T cells undergoing effector-to-memory transition including temporary upregulation of CCR5 expression and rapid downregulation of cellular gene transcription...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045904/inkt-cells-orchestrate-a-switch-from-inflammation-to-resolution-of-sterile-liver-injury
#10
Pei Xiong Liew, Woo-Yong Lee, Paul Kubes
After traumatic injury, some cells function as detectors to sense injury and to modulate the local immune response toward a restitution phase by affecting the local cytokine milieu. Using intravital microscopy, we observed that patrolling invariant natural killer T (iNKT) cells were initially excluded from a site of hepatic injury but subsequently were strategically arrested first via self-antigens and then by cytokines, circumscribing the injured site at exactly the location where monocytes co-localized and hepatocytes proliferated...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045903/hpari-protein-secreted-by-a-helminth-parasite-suppresses-interleukin-33
#11
Megan Osbourn, Dinesh C Soares, Francesco Vacca, E Suzanne Cohen, Ian C Scott, William F Gregory, Danielle J Smyth, Matilda Toivakka, Andrea M Kemter, Thierry le Bihan, Martin Wear, Dennis Hoving, Kara J Filbey, James P Hewitson, Holly Henderson, Andrea Gonzàlez-Cìscar, Claire Errington, Sonja Vermeren, Anne L Astier, William A Wallace, Jürgen Schwarze, Alasdair C Ivens, Rick M Maizels, Henry J McSorley
Infection by helminth parasites is associated with amelioration of allergic reactivity, but mechanistic insights into this association are lacking. Products secreted by the mouse parasite Heligmosomoides polygyrus suppress type 2 (allergic) immune responses through interference in the interleukin-33 (IL-33) pathway. Here, we identified H. polygyrus Alarmin Release Inhibitor (HpARI), an IL-33-suppressive 26-kDa protein, containing three predicted complement control protein (CCP) modules. In vivo, recombinant HpARI abrogated IL-33, group 2 innate lymphoid cell (ILC2) and eosinophilic responses to Alternaria allergen administration, and diminished eosinophilic responses to Nippostrongylus brasiliensis, increasing parasite burden...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045902/epidermal-growth-factor-receptor-expression-licenses-type-2-helper-t-cells-to-function-in-a-t-cell-receptor-independent-fashion
#12
Carlos M Minutti, Sebastian Drube, Natalie Blair, Christian Schwartz, Jame C McCrae, Andrew N McKenzie, Thomas Kamradt, Michal Mokry, Paul J Coffer, Maria Sibilia, Alice J Sijts, Padraic G Fallon, Rick M Maizels, Dietmar M Zaiss
Gastro-intestinal helminth infections trigger the release of interleukin-33 (IL-33), which induces type-2 helper T cells (Th2 cells) at the site of infection to produce IL-13, thereby contributing to host resistance in a T cell receptor (TCR)-independent manner. Here, we show that, as a prerequisite for IL-33-induced IL-13 secretion, Th2 cells required the expression of the epidermal growth factor receptor (EGFR) and of its ligand, amphiregulin, for the formation of a signaling complex between T1/ST2 (the IL-33R) and EGFR...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045901/by-capturing-inflammatory-lipids-released-from-dying-cells-the-receptor-cd14-induces-inflammasome-dependent-phagocyte-hyperactivation
#13
Ivan Zanoni, Yunhao Tan, Marco Di Gioia, James R Springstead, Jonathan C Kagan
A heterogeneous mixture of lipids called oxPAPC, derived from dying cells, can hyperactivate dendritic cells (DCs) but not macrophages. Hyperactive DCs are defined by their ability to release interleukin-1 (IL-1) while maintaining cell viability, endowing these cells with potent aptitude to stimulate adaptive immunity. Herein, we found that the bacterial lipopolysaccharide receptor CD14 captured extracellular oxPAPC and delivered these lipids into the cell to promote inflammasome-dependent DC hyperactivation...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045900/molecular-and-functional-characterization-of-lymphoid-progenitor-subsets-reveals-a-bipartite-architecture-of-human-lymphopoiesis
#14
Kutaiba Alhaj Hussen, Thien-Phong Vu Manh, Fabien Guimiot, Elisabeth Nelson, Emna Chabaane, Marc Delord, Maxime Barbier, Claire Berthault, Nicolas Dulphy, Antonio José Alberdi, Odile Burlen-Defranoux, Gerard Socié, Jean Christophe Bories, Jerôme Larghero, Valérie Vanneaux, Els Verhoeyen, Thierry Wirth, Marc Dalod, Jean Claude Gluckman, Ana Cumano, Bruno Canque
The classical model of hematopoiesis established in the mouse postulates that lymphoid cells originate from a founder population of common lymphoid progenitors. Here, using a modeling approach in humanized mice, we showed that human lymphoid development stemmed from distinct populations of CD127(-) and CD127(+) early lymphoid progenitors (ELPs). Combining molecular analyses with in vitro and in vivo functional assays, we demonstrated that CD127(-) and CD127(+) ELPs emerged independently from lympho-mono-dendritic progenitors, responded differently to Notch1 signals, underwent divergent modes of lineage restriction, and displayed both common and specific differentiation potentials...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045899/early-transcriptional-divergence-marks-virus-specific-primary-human-cd8-t-cells-in-chronic-versus-acute-infection
#15
David Wolski, Peter K Foote, Diana Y Chen, Lia L Lewis-Ximenez, Catherine Fauvelle, Jasneet Aneja, Andreas Walker, Pierre Tonnerre, Almudena Torres-Cornejo, Daniel Kvistad, Sabrina Imam, Michael T Waring, Damien C Tully, Todd M Allen, Raymond T Chung, Jörg Timm, W Nicholas Haining, Arthur Y Kim, Thomas F Baumert, Georg M Lauer
Distinct molecular pathways govern the differentiation of CD8(+) effector T cells into memory or exhausted T cells during acute and chronic viral infection, but these are not well studied in humans. Here, we employed an integrative systems immunology approach to identify transcriptional commonalities and differences between virus-specific CD8(+) T cells from patients with persistent and spontaneously resolving hepatitis C virus (HCV) infection during the acute phase. We observed dysregulation of metabolic processes during early persistent infection that was linked to changes in expression of genes related to nucleosomal regulation of transcription, T cell differentiation, and the inflammatory response and correlated with subject age, sex, and the presence of HCV-specific CD4(+) T cell populations...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045898/peptidoglycan-sensing-receptors-trigger-the-formation-of-functional-amyloids-of-the-adaptor-protein-imd-to-initiate-drosophila-nf-%C3%AE%C2%BAb-signaling
#16
Anni Kleino, Nancy F Ramia, Gunes Bozkurt, Yanfang Shen, Himani Nailwal, Jing Huang, Johanna Napetschnig, Monique Gangloff, Francis Ka-Ming Chan, Hao Wu, Jixi Li, Neal Silverman
In the Drosophila immune response, bacterial derived diaminopimelic acid-type peptidoglycan binds the receptors PGRP-LC and PGRP-LE, which through interaction with the adaptor protein Imd leads to activation of the NF-κB homolog Relish and robust antimicrobial peptide gene expression. PGRP-LC, PGRP-LE, and Imd each contain a motif with some resemblance to the RIP Homotypic Interaction Motif (RHIM), a domain found in mammalian RIPK proteins forming functional amyloids during necroptosis. Here we found that despite sequence divergence, these Drosophila cryptic RHIMs formed amyloid fibrils in vitro and in cells...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045897/monocyte-macrophages-and-t-cells-in-atherosclerosis
#17
REVIEW
Ira Tabas, Andrew H Lichtman
Atherosclerosis is an arterial disease process characterized by the focal subendothelial accumulation of apolipoprotein-B-containing lipoproteins, immune and vascular wall cells, and extracellular matrix. The lipoproteins acquire features of damage-associated molecular patterns and trigger first an innate immune response, dominated by monocyte-macrophages, and then an adaptive immune response. These inflammatory responses often become chronic and non-resolving and can lead to arterial damage and thrombosis-induced organ infarction...
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045896/microbes-rev-up-host-metabolism-around-the-clock
#18
Geoffrey N Pronovost, Elaine Y Hsiao
There is increasing evidence that the microbiome regulates host metabolism, but specific mechanisms underlying these interactions remain poorly understood. In a recent paper in Science, Wang et al. (2017) reveal that the gut microbiota regulates the expression of circadian-clock genes to impact host lipid metabolism and body composition.
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045895/cgas-micro-manages-genotoxic-stress
#19
Mona Motwani, Katherine A Fitzgerald
Maintenance of genome integrity is essential to prevent cancer. Genotoxic stress drives damaged DNA out of the nucleus by forming micronuclei. Two studies in Nature reveal how the cytosolic DNA sensor cGAS gains access to the cargo within micronuclei to drive type I IFN responses.
October 17, 2017: Immunity
https://www.readbyqxmd.com/read/29045894/from-oncogene-interference-to-neutrophil-immune-modulation
#20
Vincenzo Bronte
Oncogenes can aid tumor progression in a cancer cell-extrinsic way. In this issue of Immunity, Glodde et al. (2017) demonstrate that interference with c-MET tyrosine kinase receptor can relieve neutrophil-dependent immune suppression and unleash the effectiveness of immunotherapy even in the context of c-MET-independent tumors.
October 17, 2017: Immunity
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