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Immunity

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https://www.readbyqxmd.com/read/28329707/dendritic-cells-display-subset-and-tissue-specific-maturation-dynamics-over-human-life
#1
Tomer Granot, Takashi Senda, Dustin J Carpenter, Nobuhide Matsuoka, Joshua Weiner, Claire L Gordon, Michelle Miron, Brahma V Kumar, Adam Griesemer, Siu-Hong Ho, Harvey Lerner, Joseph J C Thome, Thomas Connors, Boris Reizis, Donna L Farber
Maturation and migration to lymph nodes (LNs) constitutes a central paradigm in conventional dendritic cell (cDC) biology but remains poorly defined in humans. Using our organ donor tissue resource, we analyzed cDC subset distribution, maturation, and migration in mucosal tissues (lungs, intestines), associated lymph nodes (LNs), and other lymphoid sites from 78 individuals ranging from less than 1 year to 93 years of age. The distribution of cDC1 (CD141(hi)CD13(hi)) and cDC2 (Sirp-α(+)CD1c(+)) subsets was a function of tissue site and was conserved between donors...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28329706/exposure-to-bacterial-cpg-dna-protects-from-airway-allergic-inflammation-by-expanding-regulatory-lung-interstitial-macrophages
#2
Catherine Sabatel, Coraline Radermecker, Laurence Fievez, Genevieve Paulissen, Svetoslav Chakarov, Claudia Fernandes, Sabine Olivier, Marie Toussaint, Dimitri Pirottin, Xue Xiao, Pascale Quatresooz, Jean-Claude Sirard, Didier Cataldo, Laurent Gillet, Hicham Bouabe, Christophe J Desmet, Florent Ginhoux, Thomas Marichal, Fabrice Bureau
Living in a microbe-rich environment reduces the risk of developing asthma. Exposure of humans or mice to unmethylated CpG DNA (CpG) from bacteria reproduces these protective effects, suggesting a major contribution of CpG to microbe-induced asthma resistance. However, how CpG confers protection remains elusive. We found that exposure to CpG expanded regulatory lung interstitial macrophages (IMs) from monocytes infiltrating the lung or mobilized from the spleen. Trafficking of IM precursors to the lung was independent of CCR2, a chemokine receptor required for monocyte mobilization from the bone marrow...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28329705/sensing-of-bacterial-cyclic-dinucleotides-by-the-oxidoreductase-recon-promotes-nf-%C3%AE%C2%BAb-activation-and-shapes-a-proinflammatory-antibacterial-state
#3
Adelle P McFarland, Shukun Luo, Fariha Ahmed-Qadri, Meghan Zuck, Elizabeth F Thayer, Young Ah Goo, Kevin Hybiske, Liang Tong, Joshua J Woodward
Bacterial and host cyclic dinucleotides (cdNs) mediate cytosolic immune responses through the STING signaling pathway, although evidence suggests that alternative pathways exist. We used cdN-conjugated beads to biochemically isolate host receptors for bacterial cdNs, and we identified the oxidoreductase RECON. High-affinity cdN binding inhibited RECON enzyme activity by simultaneously blocking the substrate and cosubstrate sites, as revealed by structural analyses. During bacterial infection of macrophages, RECON antagonized STING activation by acting as a molecular sink for cdNs...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28329704/the-ifn-%C3%AE-ifn-%C3%AE-r1-il-10r%C3%AE-complex-reveals-structural-features-underlying-type-iii-ifn-functional-plasticity
#4
Juan L Mendoza, William M Schneider, Hans-Heinrich Hoffmann, Koen Vercauteren, Kevin M Jude, Anming Xiong, Ignacio Moraga, Tim M Horton, Jeffrey S Glenn, Ype P de Jong, Charles M Rice, K Christopher Garcia
Type III interferons (IFN-λs) signal through a heterodimeric receptor complex composed of the IFN-λR1 subunit, specific for IFN-λs, and interleukin-10Rβ (IL-10Rβ), which is shared by multiple cytokines in the IL-10 superfamily. Low affinity of IL-10Rβ for cytokines has impeded efforts aimed at crystallizing cytokine-receptor complexes. We used yeast surface display to engineer a higher-affinity IFN-λ variant, H11, which enabled crystallization of the ternary complex. The structure revealed that IL-10Rβ uses a network of tyrosine residues as hydrophobic anchor points to engage IL-10 family cytokines that present complementary hydrophobic binding patches, explaining its role as both a cross-reactive but cytokine-specific receptor...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28329703/successful-and-maladaptive-t-cell-aging
#5
REVIEW
Jörg J Goronzy, Cornelia M Weyand
Throughout life, the T cell system adapts to shifting resources and demands, resulting in a fundamentally restructured immune system in older individuals. Here we review the cellular and molecular features of an aged immune system and discuss the trade-offs inherent to these adaptive mechanisms. Processes include homeostatic proliferation that maintains compartment size at the expense of partial loss in stemness and incomplete differentiation and the activation of negative regulatory programs, which constrain effector T cell expansion and prevent increasing oligoclonality but also interfere with memory cell generation...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28329702/protecting-the-newborn-and-young-infant-from-infectious-diseases-lessons-from-immune-ontogeny
#6
REVIEW
Tobias R Kollmann, Beate Kampmann, Sarkis K Mazmanian, Arnaud Marchant, Ofer Levy
Infections in the first year of life are common and often severe. The newborn host demonstrates both quantitative and qualitative differences to the adult in nearly all aspects of immunity, which at least partially explain the increased susceptibility to infection. Here we discuss how differences in susceptibility to infection result not out of a state of immaturity, but rather reflect adaptation to the particular demands placed on the immune system in early life. We review the mechanisms underlying host defense in the very young, and discuss how specific developmental demands increase the risk of particular infectious diseases...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28329701/interleukin-17-why-the-worms-squirm
#7
Noah J Silverstein, Jun R Huh
IL-17 is a cytokine known primarily for its role in inflammation. In a recent issue of Nature, Chen et al. (2017) demonstrate that IL-17 plays a neuromodulatory role in Caenorhabditis elegans by acting directly on neurons to amplify neuronal responses to stimuli and produce changes in animal behavior.
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28329700/ilc-poiesis-making-tissue-ilcs-from-blood
#8
Jenny Mjösberg, Luca Mazzurana
The development of human innate lymphoid cells (ILCs) remains poorly characterized. In a recent issue of Cell, Lim et al. show that human peripheral-blood CD117(+) ILCs harbor ILC precursors (ILCPs) derived from hematopoietic stem cells. Peripheral-blood ILCPs can generate all ILC subsets in vivo and in vitro.
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28329699/of-human-dc-migrants-and-residents
#9
Elodie Segura, Vassili Soumelis
Migration from peripheral tissues to lymph nodes is a key feature of dendritic cells (DCs), but little is known about the migration patterns of human DCs. By analyzing multiple lymphoid organs and tissues from the same donors, Granot et al. propose that the two main subsets of human DCs display different migratory capacity.
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28329698/disarming-the-killers-brain-strikes-on-nk-cells
#10
Linda Quatrini, Sophie Ugolini
Brain ischemia induces profound systemic immunosuppression, leading to infectious complications. In this issue of Immunity, Liu et al. (2017) demonstrate that distinct neuroendocrine pathways differentially inhibit natural killer (NK) cell responses in the central nervous system and the periphery after cerebral infarction.
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28329697/reconsidering-sensing-of-cyclic-dinucleotides
#11
Jonathan Maelfait, Jan Rehwinkel
Detection of cyclic dinucleotides (cdNs) by the STING pathway potently triggers the antiviral response. McFarland et al. now show that the mouse oxidoreductase RECON acts as a sensor for some bacterial cdNs, modulating innate signaling in a manner independent of STING to promote an antibacterial state.
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28329696/neutrophils-across-the-enemy-lines
#12
Carlos Del Fresno, Andrés Hidalgo
In this issue of Immunity, Warnatsch et al. (2017) describe how neutrophils measure their microbial opponents by differential shuttling of reactive oxygen species (ROS), a process that determines their recruitment and distribution and ultimately the strength of anti-microbial responses.
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28329695/cutting-edge-in-ifn-regulation-inflammatory-caspases-cleave-cgas
#13
Simon Heidegger, Tobias Haas, Hendrik Poeck
Caspases have important functions beyond their established role in driving inflammation and apoptosis. In this issue of Immunity, Wang et al. (2017) demonstrate that inflammasome-triggered caspases cleave and inactivate the DNA sensor cGAS, thus restricting the type I interferon response to cytosolic DNA.
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28329694/the-ilc-world-revisited
#14
Andreas Diefenbach, Marco Colonna, Chiara Romagnani
Immunology has recently witnessed several new developments in understanding the biology of innate lymphocytes. In particular, the discovery of innate lymphoid cells (ILCs) has opened entirely new avenues for research. The exciting new developments in this rapidly expanding field were the focus of the 2(nd)EMBO Conference on Innate Lymphoid Cells, which took place from November 30 to December 2, 2016 in Berlin, Germany. Here, we summarize the key new developments reported at the conference.
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28314594/brain-ischemia-suppresses-immunity-in-the-periphery-and-brain-via-different-neurogenic-innervations
#15
Qiang Liu, Wei-Na Jin, Yaou Liu, Kaibin Shi, Haoran Sun, Fang Zhang, Chao Zhang, Rayna J Gonzales, Kevin N Sheth, Antonio La Cava, Fu-Dong Shi
Brain ischemia inhibits immune function systemically, with resulting infectious complications. Whether in stroke different immune alterations occur in brain and periphery and whether analogous mechanisms operate in these compartments remains unclear. Here we show that in patients with ischemic stroke and in mice subjected to middle cerebral artery occlusion, natural killer (NK) cells display remarkably distinct temporal and transcriptome profiles in the brain as compared to the periphery. The activation of catecholaminergic and hypothalamic-pituitary-adrenal axis leads to splenic atrophy and contraction of NK cell numbers in the periphery through a modulated expression of SOCS3, whereas cholinergic innervation-mediated suppression of NK cell responses in the brain involves RUNX3...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28314593/25-hydroxycholesterol-protects-host-against-zika-virus-infection-and-its-associated-microcephaly-in-a-mouse-model
#16
Chunfeng Li, Yong-Qiang Deng, Shuo Wang, Feng Ma, Roghiyh Aliyari, Xing-Yao Huang, Na-Na Zhang, Momoko Watanabe, Hao-Long Dong, Ping Liu, Xiao-Feng Li, Qing Ye, Min Tian, Shuai Hong, Junwan Fan, Hui Zhao, Lili Li, Neda Vishlaghi, Jessie E Buth, Connie Au, Ying Liu, Ning Lu, Peishuang Du, F Xiao-Feng Qin, Bo Zhang, Danyang Gong, Xinghong Dai, Ren Sun, Bennett G Novitch, Zhiheng Xu, Cheng-Feng Qin, Genhong Cheng
Zika virus (ZIKV) has become a public health threat due to its global transmission and link to severe congenital disorders. The host immune responses to ZIKV infection have not been fully elucidated, and effective therapeutics are not currently available. Herein, we demonstrated that cholesterol-25-hydroxylase (CH25H) was induced in response to ZIKV infection and that its enzymatic product, 25-hydroxycholesterol (25HC), was a critical mediator of host protection against ZIKV. Synthetic 25HC addition inhibited ZIKV infection in vitro by blocking viral entry, and treatment with 25HC reduced viremia and conferred protection against ZIKV in mice and rhesus macaques...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28314592/reactive-oxygen-species-localization-programs-inflammation-to-clear-microbes-of-different-size
#17
Annika Warnatsch, Theodora-Dorita Tsourouktsoglou, Nora Branzk, Qian Wang, Susanna Reincke, Susanne Herbst, Maximiliano Gutierrez, Venizelos Papayannopoulos
How the number of immune cells recruited to sites of infection is determined and adjusted to differences in the cellular stoichiometry between host and pathogen is unknown. Here, we have uncovered a role for reactive oxygen species (ROS) as sensors of microbe size. By sensing the differential localization of ROS generated in response to microbes of different size, neutrophils tuned their interleukin (IL)-1β expression via the selective oxidation of NF-κB, in order to implement distinct inflammatory programs...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28314591/the-ubiquitin-binding-protein-tax1bp1-mediates-autophagasome-induction-and-the-metabolic-transition-of-activated-t-cells
#18
Michael I Whang, Rita M Tavares, Daniel I Benjamin, Michael G Kattah, Rommel Advincula, Daniel K Nomura, Jayanta Debnath, Barbara A Malynn, Averil Ma
During immune responses, naive T cells transition from small quiescent cells to rapidly cycling cells. We have found that T cells lacking TAX1BP1 exhibit delays in growth of cell size and cell cycling. TAX1BP1-deficient T cells exited G0 but stalled in S phase, due to both bioenergetic and biosynthetic defects. These defects were due to deficiencies in mTOR complex formation and activation. These mTOR defects in turn resulted from defective autophagy induction. TAX1BP1 binding of LC3 and GABARAP via its LC3-interacting region (LIR), but not its ubiquitin-binding domain, supported T cell proliferation...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28314590/inflammasome-activation-triggers-caspase-1-mediated-cleavage-of-cgas-to-regulate-responses-to-dna-virus-infection
#19
Yutao Wang, Xiaohan Ning, Pengfei Gao, Shuxian Wu, Mengyin Sha, Mengze Lv, Xiang Zhou, Juyi Gao, Run Fang, Guangxun Meng, Xiaodong Su, Zhengfan Jiang
Viral infection triggers host innate immune responses that result in the production of various cytokines including type I interferons (IFN), activation of inflammasomes, and programmed cell death of the infected cells. Tight control of inflammatory cytokine production is crucial for the triggering of an effective immune response that can resolve the infection without causing host pathology. In examining the inflammatory response of Asc(-/-) and Casp1(-/-) macrophages, we found that deficiency in these molecules resulted in increased IFN production upon DNA virus infection, but not RNA virus challenge...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28285833/integrative-proteomics-and-phosphoproteomics-profiling-reveals-dynamic-signaling-networks-and-bioenergetics-pathways-underlying-t-cell-activation
#20
Haiyan Tan, Kai Yang, Yuxin Li, Timothy I Shaw, Yanyan Wang, Daniel Bastardo Blanco, Xusheng Wang, Ji-Hoon Cho, Hong Wang, Sherri Rankin, Cliff Guy, Junmin Peng, Hongbo Chi
The molecular circuits by which antigens activate quiescent T cells remain poorly understood. We combined temporal profiling of the whole proteome and phosphoproteome via multiplexed isobaric labeling proteomics technology, computational pipelines for integrating multi-omics datasets, and functional perturbation to systemically reconstruct regulatory networks underlying T cell activation. T cell receptors activated the T cell proteome and phosphoproteome with discrete kinetics, marked by early dynamics of phosphorylation and delayed ribosome biogenesis and mitochondrial activation...
March 21, 2017: Immunity
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