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Immunity

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https://www.readbyqxmd.com/read/28636969/human-virus-derived-small-rnas-can-confer-antiviral-immunity-in-mammals
#1
Yang Qiu, Yanpeng Xu, Yao Zhang, Hui Zhou, Yong-Qiang Deng, Xiao-Feng Li, Meng Miao, Qiang Zhang, Bo Zhong, Yuanyang Hu, Fu-Chun Zhang, Ligang Wu, Cheng-Feng Qin, Xi Zhou
RNA interference (RNAi) functions as a potent antiviral immunity in plants and invertebrates; however, whether RNAi plays antiviral roles in mammals remains unclear. Here, using human enterovirus 71 (HEV71) as a model, we showed HEV71 3A protein as an authentic viral suppressor of RNAi during viral infection. When the 3A-mediated RNAi suppression was impaired, the mutant HEV71 readily triggered the production of abundant HEV71-derived small RNAs with canonical siRNA properties in cells and mice. These virus-derived siRNAs were produced from viral dsRNA replicative intermediates in a Dicer-dependent manner and loaded into AGO, and they were fully active in degrading cognate viral RNAs...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636968/t-regulating-hair-follicle-stem-cells
#2
Maria Maryanovich, Paul S Frenette
Regulatory T (Treg) cells are well known to modulate inflammatory responses. In a recent issue of Cell, Ali et al. (2017) reveal a function for Treg cells in stem cell maintenance by showing that skin-resident Foxp3(+) Treg cells preferentially localize to the hair follicle stem cell (HFSC) niche to control HFSC-mediated hair regeneration.
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636967/a-few-good-commensals-gut-microbes-use-ifn-%C3%AE-to-fight-salmonella
#3
Kyla S Ost, June L Round
Whereas strong evidence supports the notion that the microbiota promotes immune system maturation in multiple tissues, the identity of the specific microbes that elicit protective immunity to different infections is less clear. In a recent issue of Cell Host & Microbe, Thiemann et al. (2017) report the identification of specific gut bacteria that protect from Salmonella infection by priming host IFN-γ responses.
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636966/the-torc-that-gets-the-gc-cycling
#4
Elissa K Deenick, Stuart G Tangye
The signaling pathways regulating positive selection in germinal centers (GCs) are incompletely understood. Ersching et al. (2017) identify a critical but temporal role for the action of the kinase mechanistic target of rapamycin complex (mTORC1), which promotes key changes in GC B cells and thereby facilitates affinity maturation.
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636965/hla-f-a-new-kid-licensed-for-peptide-presentation
#5
Malcolm J W Sim, Peter D Sun
HLA-F, a non-classical MHC molecule, is not known to present peptides. Dulberger et al. (2017) show that HLA-F contains a distinct peptide-binding groove and can present a diverse array of peptides. LIR1, however, recognized HLA-F away from bound peptide, leaving open whether peptide-HLA-F-specific T and NK receptors exist.
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636964/rna-interference-in-mammals-the-virus-strikes-back
#6
Bryan R Cullen
The importance of RNA interference (RNAi) as a mammalian antiviral defense mechanism has been controversial. Qiu et al. (2017) now present data suggesting that the difficulty of detecting RNAi in virus-infected mammalian cells reflects the expression of highly effective viral suppressors of RNAi.
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636963/t-bet-runs-interference
#7
Vanja Lazarevic, Susanne Szabo, Laurie H Glimcher
In this issue of Immunity, Iwata et al. (2017) report that the transcription factor T-bet acts as a selective repressor of the type I interferon (IFN) transcriptional program in response to IFN-γ signaling.
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636962/reactive-astrocytes-production-function-and-therapeutic-potential
#8
REVIEW
Shane A Liddelow, Ben A Barres
Astrocytes constitute approximately 30% of the cells in the mammalian central nervous system (CNS). They are integral to brain and spinal-cord physiology and perform many functions important for normal neuronal development, synapse formation, and proper propagation of action potentials. We still know very little, however, about how these functions change in response to immune attack, chronic neurodegenerative disease, or acute trauma. In this review, we summarize recent studies that demonstrate that different initiating CNS injuries can elicit at least two types of "reactive" astrocytes with strikingly different properties, one type being helpful and the other harmful...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636961/myeloid-cells-in-the-central-nervous-system
#9
REVIEW
Jasmin Herz, Anthony J Filiano, Ashtyn Smith, Nir Yogev, Jonathan Kipnis
The central nervous system (CNS) and its meningeal coverings accommodate a diverse myeloid compartment that includes parenchymal microglia and perivascular macrophages, as well as choroid plexus and meningeal macrophages, dendritic cells, and granulocytes. These myeloid populations enjoy an intimate relationship with the CNS, where they play an essential role in both health and disease. Although the importance of these cells is clearly recognized, their exact function in the CNS continues to be explored. Here, we review the subsets of myeloid cells that inhabit the parenchyma, meninges, and choroid plexus and discuss their roles in CNS homeostasis...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636960/mechanisms-and-therapeutic-relevance-of-neuro-immune-communication
#10
REVIEW
Sangeeta S Chavan, Valentin A Pavlov, Kevin J Tracey
Active research at the frontiers of immunology and neuroscience has identified multiple points of interaction and communication between the immune system and the nervous system. Immune cell activation stimulates neuronal circuits that regulate innate and adaptive immunity. Molecular mechanistic insights into the inflammatory reflex and other neuro-immune interactions have greatly advanced our understanding of immunity and identified new therapeutic possibilities in inflammatory and autoimmune diseases. Recent successful clinical trials using bioelectronic devices that modulate the inflammatory reflex to significantly ameliorate rheumatoid arthritis and inflammatory bowel disease provide a path for using electrons as a therapeutic modality for targeting molecular mechanisms of immunity...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636959/the-enteric-network-interactions-between-the-immune-and-nervous-systems-of-the-gut
#11
REVIEW
Bryan B Yoo, Sarkis K Mazmanian
Interactions between the nervous and immune systems enable the gut to respond to the variety of dietary products that it absorbs, the broad spectrum of pathogens that it encounters, and the diverse microbiome that it harbors. The enteric nervous system (ENS) senses and reacts to the dynamic ecosystem of the gastrointestinal (GI) tract by translating chemical cues from the environment into neuronal impulses that propagate throughout the gut and into other organs in the body, including the central nervous system (CNS)...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636958/protective-and-pathological-immunity-during-central-nervous-system-infections
#12
REVIEW
Robyn S Klein, Christopher A Hunter
The concept of immune privilege of the central nervous system (CNS) has dominated the study of inflammatory processes in the brain. However, clinically relevant models have highlighted that innate pathways limit pathogen invasion of the CNS and adaptive immunity mediates control of many neural infections. As protective responses can result in bystander damage, there are regulatory mechanisms that balance protective and pathological inflammation, but these mechanisms might also allow microbial persistence. The focus of this review is to consider the host-pathogen interactions that influence neurotropic infections and to highlight advances in our understanding of innate and adaptive mechanisms of resistance as key determinants of the outcome of CNS infection...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636957/glutathione-primes-t-cell-metabolism-for-inflammation
#13
Tak W Mak, Melanie Grusdat, Gordon S Duncan, Catherine Dostert, Yannic Nonnenmacher, Maureen Cox, Carole Binsfeld, Zhenyue Hao, Anne Brüstle, Momoe Itsumi, Christian Jäger, Ying Chen, Olaf Pinkenburg, Bärbel Camara, Markus Ollert, Carsten Bindslev-Jensen, Vasilis Vasiliou, Chiara Gorrini, Philipp A Lang, Michael Lohoff, Isaac S Harris, Karsten Hiller, Dirk Brenner
No abstract text is available yet for this article.
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636956/elicitation-of-robust-tier-2-neutralizing-antibody-responses-in-nonhuman-primates-by-hiv-envelope-trimer-immunization-using-optimized-approaches
#14
Matthias Pauthner, Colin Havenar-Daughton, Devin Sok, Joseph P Nkolola, Raiza Bastidas, Archana V Boopathy, Diane G Carnathan, Abishek Chandrashekar, Kimberly M Cirelli, Christopher A Cottrell, Alexey M Eroshkin, Javier Guenaga, Kirti Kaushik, Daniel W Kulp, Jinyan Liu, Laura E McCoy, Aaron L Oom, Gabriel Ozorowski, Kai W Post, Shailendra K Sharma, Jon M Steichen, Steven W de Taeye, Talar Tokatlian, Alba Torrents de la Peña, Salvatore T Butera, Celia C LaBranche, David C Montefiori, Guido Silvestri, Ian A Wilson, Darrell J Irvine, Rogier W Sanders, William R Schief, Andrew B Ward, Richard T Wyatt, Dan H Barouch, Shane Crotty, Dennis R Burton
The development of stabilized recombinant HIV envelope trimers that mimic the virion surface molecule has increased enthusiasm for a neutralizing antibody (nAb)-based HIV vaccine. However, there is limited experience with recombinant trimers as immunogens in nonhuman primates, which are typically used as a model for humans. Here, we tested multiple immunogens and immunization strategies head-to-head to determine their impact on the quantity, quality, and kinetics of autologous tier 2 nAb development. A bilateral, adjuvanted, subcutaneous immunization protocol induced reproducible tier 2 nAb responses after only two immunizations 8 weeks apart, and these were further enhanced by a third immunization with BG505 SOSIP trimer...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636955/inflammatory-ly6c-high-monocytes-protect-against-candidiasis-through-il-15-driven-nk-cell-neutrophil-activation
#15
Jorge Domínguez-Andrés, Lidia Feo-Lucas, María Minguito de la Escalera, Leticia González, María López-Bravo, Carlos Ardavín
Neutrophils play a crucial role in defense against systemic candidiasis, a disease associated with a high mortality rate in patients receiving immunosuppressive therapy, although the early immune mechanisms that boost the candidacidal activity of neutrophils remain to be defined in depth. Here, we used a murine model of systemic candidiasis to explore the role of inflammatory Ly6C(high) monocytes in NK cell-mediated neutrophil activation during the innate immune response against C. albicans. We found that efficient anti-Candida immunity required a collaborative response between the spleen and kidney, which relied on type I interferon-dependent IL-15 production by spleen inflammatory Ly6C(high) monocytes to drive efficient activation and GM-CSF release by spleen NK cells; this in turn was necessary to boost the Candida killing potential of kidney neutrophils...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636954/germinal-center-selection-and-affinity-maturation-require-dynamic-regulation-of-mtorc1-kinase
#16
Jonatan Ersching, Alejo Efeyan, Luka Mesin, Johanne T Jacobsen, Giulia Pasqual, Brian C Grabiner, David Dominguez-Sola, David M Sabatini, Gabriel D Victora
During antibody affinity maturation, germinal center (GC) B cells cycle between affinity-driven selection in the light zone (LZ) and proliferation and somatic hypermutation in the dark zone (DZ). Although selection of GC B cells is triggered by antigen-dependent signals delivered in the LZ, DZ proliferation occurs in the absence of such signals. We show that positive selection triggered by T cell help activates the mechanistic target of rapamycin complex 1 (mTORC1), which promotes the anabolic program that supports DZ proliferation...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636953/dicer-deficiency-differentially-impacts-microglia-of-the-developing-and-adult-brain
#17
Diana Varol, Alexander Mildner, Thomas Blank, Anat Shemer, Neta Barashi, Simon Yona, Eyal David, Sigalit Boura-Halfon, Yifat Segal-Hayoun, Louise Chappell-Maor, Hadas Keren-Shaul, Dena Leshkowitz, Eran Hornstein, Martin Fuhrmann, Ido Amit, Nicola Maggio, Marco Prinz, Steffen Jung
Microglia seed the embryonic neuro-epithelium, expand and actively sculpt neuronal circuits in the developing central nervous system, but eventually adopt relative quiescence and ramified morphology in the adult. Here, we probed the impact of post-transcriptional control by microRNAs (miRNAs) on microglial performance during development and adulthood by generating mice lacking microglial Dicer expression at these distinct stages. Conditional Dicer ablation in adult microglia revealed that miRNAs were required to limit microglial responses to challenge...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636952/human-leukocyte-antigen-f-presents-peptides-and-regulates-immunity-through-interactions-with-nk-cell-receptors
#18
Charles L Dulberger, Curtis P McMurtrey, Angelique Hölzemer, Karlynn E Neu, Victor Liu, Adriana M Steinbach, Wilfredo F Garcia-Beltran, Michael Sulak, Bana Jabri, Vincent J Lynch, Marcus Altfeld, William H Hildebrand, Erin J Adams
Evidence is mounting that the major histocompatibility complex (MHC) molecule HLA-F (human leukocyte antigen F) regulates the immune system in pregnancy, infection, and autoimmunity by signaling through NK cell receptors (NKRs). We present structural, biochemical, and evolutionary analyses demonstrating that HLA-F presents peptides of unconventional length dictated by a newly arisen mutation (R62W) that has produced an open-ended groove accommodating particularly long peptides. Compared to empty HLA-F open conformers (OCs), HLA-F tetramers bound with human-derived peptides differentially stained leukocytes, suggesting peptide-dependent engagement...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28636951/structure-of-cc-chemokine-receptor-5-with-a-potent-chemokine-antagonist-reveals-mechanisms-of-chemokine-recognition-and-molecular-mimicry-by-hiv
#19
Yi Zheng, Gye Won Han, Ruben Abagyan, Beili Wu, Raymond C Stevens, Vadim Cherezov, Irina Kufareva, Tracy M Handel
CCR5 is the primary chemokine receptor utilized by HIV to infect leukocytes, whereas CCR5 ligands inhibit infection by blocking CCR5 engagement with HIV gp120. To guide the design of improved therapeutics, we solved the structure of CCR5 in complex with chemokine antagonist [5P7]CCL5. Several structural features appeared to contribute to the anti-HIV potency of [5P7]CCL5, including the distinct chemokine orientation relative to the receptor, the near-complete occupancy of the receptor binding pocket, the dense network of intermolecular hydrogen bonds, and the similarity of binding determinants with the FDA-approved HIV inhibitor Maraviroc...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28623086/the-transcription-factor-t-bet-limits-amplification-of-type-i-ifn-transcriptome-and-circuitry-in-t-helper-1-cells
#20
Shigeru Iwata, Yohei Mikami, Hong-Wei Sun, Stephen R Brooks, Dragana Jankovic, Kiyoshi Hirahara, Atsushi Onodera, Han-Yu Shih, Takeshi Kawabe, Kan Jiang, Toshinori Nakayama, Alan Sher, John J O'Shea, Fred P Davis, Yuka Kanno
Host defense requires the specification of CD4(+) helper T (Th) cells into distinct fates, including Th1 cells that preferentially produce interferon-γ (IFN-γ). IFN-γ, a member of a large family of anti-pathogenic and anti-tumor IFNs, induces T-bet, a lineage-defining transcription factor for Th1 cells, which in turn supports IFN-γ production in a feed-forward manner. Herein, we show that a cell-intrinsic role of T-bet influences how T cells perceive their secreted product in the environment. In the absence of T-bet, IFN-γ aberrantly induced a type I IFN transcriptomic program...
June 20, 2017: Immunity
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