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Immunity

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https://www.readbyqxmd.com/read/28723556/peroxisome-mediated-metabolism-is-required-for-immune-response-to-microbial-infection
#1
Francesca Di Cara, Avinash Sheshachalam, Nancy E Braverman, Richard A Rachubinski, Andrew J Simmonds
The innate immune response is critical for animal homeostasis and is conserved from invertebrates to vertebrates. This response depends on specialized cells that recognize, internalize, and destroy microbial invaders through phagocytosis. This is coupled to autonomous or non-autonomous cellular signaling via reactive oxygen species (ROS) and cytokine production. Lipids are known signaling factors in this process, as the acute phase response of macrophages is accompanied by systemic lipid changes that help resolve inflammation...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28723555/ilcs-and-t-cells-competing-for-space-more-than-a-numbers-game
#2
Christin Friedrich, Georg Gasteiger
T cell homeostasis critically depends on interleukin-7 (IL-7). In this issue of Immunity, Martin et al. (2017) provide evidence that IL-7 availability is regulated through a "cytokine sink" involving innate lymphoid cells that compete for and consume IL-7 and thereby restrict T cell homeostasis in lymphoid organs.
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28723554/hypoxia-sensitive-commd1-integrates-signaling-and-cellular-metabolism-in-human-macrophages-and-suppresses-osteoclastogenesis
#3
Koichi Murata, Celestia Fang, Chikashi Terao, Eugenia G Giannopoulou, Ye Ji Lee, Min Joon Lee, Se-Hwan Mun, Seyeon Bae, Yu Qiao, Ruoxi Yuan, Moritoshi Furu, Hiromu Ito, Koichiro Ohmura, Shuichi Matsuda, Tsuneyo Mimori, Fumihiko Matsuda, Kyung-Hyun Park-Min, Lionel B Ivashkiv
Hypoxia augments inflammatory responses and osteoclastogenesis by incompletely understood mechanisms. We identified COMMD1 as a cell-intrinsic negative regulator of osteoclastogenesis that is suppressed by hypoxia. In human macrophages, COMMD1 restrained induction of NF-κB signaling and a transcription factor E2F1-dependent metabolic pathway by the cytokine RANKL. Downregulation of COMMD1 protein expression by hypoxia augmented RANKL-induced expression of inflammatory and E2F1 target genes and downstream osteoclastogenesis...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28723553/a-commencement-for-eye-commensals
#4
Nancy J Reyes, Daniel R Saban
"Paucibacterial" levels of the normal eye surface have left immunologists wondering whether a true microbiome exists there. In this issue of Immunity, St. Leger et al. (2017) address this head-on, discovering a naturally existing commensal in mice that induces γδT cell-mediated protection from opportunistic infection.
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28723552/immunology-of-food-allergy
#5
REVIEW
Leticia Tordesillas, M Cecilia Berin, Hugh A Sampson
Many consider food allergy as the "second wave" of the allergy epidemic following the "first wave" of respiratory allergy, i.e., asthma and allergic rhinitis, plaguing westernized countries, with up to 8% of young children and 2%-3% of adults in the United States now affected by hypersensitivity reactions to various foods. In the past decade, there have been great strides in our understanding of the underlying immunopathogenesis of these disorders, which have led to improved diagnostic techniques, management strategies, and therapeutic approaches...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28723551/understanding-immunosuppression-after-sepsis
#6
Fatemeh Fattahi, Peter A Ward
Following a severe primary infection or trauma, the risk of developing pneumonia increases due to acquired immune defects collectively known as sepsis-induced immunosuppression. In this issue of Immunity, Roquilly et al. (2017) show that dendritic cells and macrophages developing in the lung after the resolution of a severe infection acquire tolerogenic properties that contribute to persistent immunosuppression and susceptibility to secondary infections.
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28723550/induced-pluripotent-stem-cell-derived-primitive-macrophages-provide-a-platform-for-modeling-tissue-resident-macrophage-differentiation-and-function
#7
Kazuyuki Takata, Tatsuya Kozaki, Christopher Zhe Wei Lee, Morgane Sonia Thion, Masayuki Otsuka, Shawn Lim, Kagistia Hana Utami, Kerem Fidan, Dong Shin Park, Benoit Malleret, Svetoslav Chakarov, Peter See, Donovan Low, Gillian Low, Marta Garcia-Miralles, Ruizhu Zeng, Jinqiu Zhang, Chi Ching Goh, Ahmet Gul, Sandra Hubert, Bernett Lee, Jinmiao Chen, Ivy Low, Nurhidaya Binte Shadan, Josephine Lum, Tay Seok Wei, Esther Mok, Shohei Kawanishi, Yoshihisa Kitamura, Anis Larbi, Michael Poidinger, Laurent Renia, Lai Guan Ng, Yochai Wolf, Steffen Jung, Tamer Önder, Evan Newell, Tara Huber, Eishi Ashihara, Sonia Garel, Mahmoud A Pouladi, Florent Ginhoux
Tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that give rise to primitive YS macrophages. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMacs) can terminally differentiate into specialized macrophages with the help of growth factors and organ-specific cues...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28723549/interleukin-7-availability-is-maintained-by-a-hematopoietic-cytokine-sink-comprising-innate-lymphoid-cells-and-t%C3%A2-cells
#8
Christopher E Martin, Darina S Spasova, Kwesi Frimpong-Boateng, Hee-Ok Kim, Minji Lee, Kwang Soon Kim, Charles D Surh
Interleukin-7 (IL-7) availability determines the size and proliferative state of the resting T cell pool. However, the mechanisms that regulate steady-state IL-7 amounts are unclear. Using experimental lymphopenic mouse models and IL-7-induced homeostatic proliferation to measure IL-7 availability in vivo, we found that radioresistant cells were the source of IL-7 for both CD4(+) and CD8(+) T cells. Hematopoietic lineage cells, although irrelevant as a source of IL-7, were primarily responsible for limiting IL-7 availability via their expression of IL-7R...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28723548/the-fc-domain-of-immunoglobulin-is-sufficient-to-bridge-nk-cells-with-virally-infected-cells
#9
Hong-Sheng Dai, Nathaniel Griffin, Chelsea Bolyard, Hsiaoyin Charlene Mao, Jianying Zhang, Timothy P Cripe, Tadahiro Suenaga, Hisashi Arase, Ichiro Nakano, E A Chiocca, Balveen Kaur, Jianhua Yu, Michael A Caligiuri
Clearance of pathogens or tumor cells by antibodies traditionally requires both Fab and Fc domains of IgG. Here, we show the Fc domain of IgG alone mediates recognition and clearance of herpes simplex virus (HSV1)-infected cells. The human natural killer (NK) cell surface is naturally coated with IgG bound by its Fc domain to the Fcγ receptor CD16a. NK cells utilize the Fc domain of bound IgG to recognize gE, an HSV1-encoded glycoprotein that also binds the Fc domain of IgG but at a site distinct from CD16a...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28723547/the-p2x7-receptor-in-infection-and-inflammation
#10
REVIEW
Francesco Di Virgilio, Diego Dal Ben, Alba Clara Sarti, Anna Lisa Giuliani, Simonetta Falzoni
Adenosine triphosphate (ATP) accumulates at sites of tissue injury and inflammation. Effects of extracellular ATP are mediated by plasma membrane receptors named P2 receptors (P2Rs). The P2R most involved in inflammation and immunity is the P2X7 receptor (P2X7R), expressed by virtually all cells of innate and adaptive immunity. P2X7R mediates NLRP3 inflammasome activation, cytokine and chemokine release, T lymphocyte survival and differentiation, transcription factor activation, and cell death. Ten human P2RX7 gene splice variants and several SNPs that produce complex haplotypes are known...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28723546/local-modulation-of-antigen-presenting-cell-development-after-resolution-of-pneumonia-induces-long-term-susceptibility-to-secondary-infections
#11
Antoine Roquilly, Hamish E G McWilliam, Cedric Jacqueline, Zehua Tian, Raphael Cinotti, Marie Rimbert, Linda Wakim, Irina Caminschi, Mireille H Lahoud, Gabrielle T Belz, Axel Kallies, Justine D Mintern, Karim Asehnoune, Jose A Villadangos
Lung infections cause prolonged immune alterations and elevated susceptibility to secondary pneumonia. We found that, after resolution of primary viral or bacterial pneumonia, dendritic cells (DC), and macrophages exhibited poor antigen-presentation capacity and secretion of immunogenic cytokines. Development of these "paralyzed" DCs and macrophages depended on the immunosuppressive microenvironment established upon resolution of primary infection, which involved regulatory T (Treg) cells and the cytokine TGF-β...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28723545/spineless-behavior-of-cx3cr1-monocytes-in-response-to-infection
#12
Paul A Muller, Daniel Mucida
Sickness in mammals can lead to cognition deficits, although the underlying mechanisms remain elusive. In a recent Nature Medicine article, Garré et al. (2017) report that sickness-induced cortical dendritic spine loss and impaired memory formation is mediated by CX3CR1(+) monocyte-derived TNF-α.
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28723544/upgrading-from-imac-to-imicro
#13
Alma N Mohebiany, Ari Waisman
In this issue of Immunity, Takata et al. (2017) describe a novel method to differentiate macrophages from iPSCs. These cells, which they call iMacs, are similar to yolk-sac-derived macrophages and are capable of undergoing terminal differentiation into tissue-resident-like macrophages in vitro and in vivo.
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28723543/necroptosis-last-message-in-a-bubble
#14
Peter Vandenabeele, Franck Riquet, Benjamin Cappe
RIPK3 kinase-mediated phosphorylation of MLKL pseudokinase is the execution event of necroptosis. Two independent reports-in Immunity (Yoon et al., 2017) and Cell (Gong et al., 2017)-reveal that MLKL affects homeostatic membrane trafficking and necroptosis-enhanced bubble formation involving interaction with the ESCRT machinery.
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28709804/identification-of-natural-regulatory-t-cell-epitopes-reveals-convergence-on-a-dominant-autoantigen
#15
John D Leonard, Dana C Gilmore, Thamotharampillai Dileepan, Wioletta I Nawrocka, Jaime L Chao, Mary H Schoenbach, Marc K Jenkins, Erin J Adams, Peter A Savage
Regulatory T (Treg) cells expressing the transcription factor Foxp3 are critical for the prevention of autoimmunity and the suppression of anti-tumor immunity. The major self-antigens recognized by Treg cells remain undefined, representing a substantial barrier to the understanding of immune regulation. Here, we have identified natural Treg cell ligands in mice. We found that two recurrent Treg cell clones, one prevalent in prostate tumors and the other associated with prostatic autoimmune lesions, recognized distinct non-overlapping MHC-class-II-restricted peptides derived from the same prostate-specific protein...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28709803/an-ocular-commensal-protects-against-corneal-infection-by-driving-an-interleukin-17-response-from-mucosal-%C3%AE-%C3%AE-t-cells
#16
Anthony J St Leger, Jigar V Desai, Rebecca A Drummond, Abirami Kugadas, Fatimah Almaghrabi, Phyllis Silver, Kumarkrishna Raychaudhuri, Mihaela Gadjeva, Yoichiro Iwakura, Michail S Lionakis, Rachel R Caspi
Mucosal sites such as the intestine, oral cavity, nasopharynx, and vagina all have associated commensal flora. The surface of the eye is also a mucosal site, but proof of a living, resident ocular microbiome remains elusive. Here, we used a mouse model of ocular surface disease to reveal that commensals were present in the ocular mucosa and had functional immunological consequences. We isolated one such candidate commensal, Corynebacterium mastitidis, and showed that this organism elicited a commensal-specific interleukin-17 response from γδ T cells in the ocular mucosa that was central to local immunity...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28709802/human-secretory-igm-emerges-from-plasma-cells-clonally-related-to-gut-memory-b-cells-and-targets-highly-diverse-commensals
#17
Giuliana Magri, Laura Comerma, Marc Pybus, Jordi Sintes, David Lligé, Daniel Segura-Garzón, Sabrina Bascones, Ada Yeste, Emilie K Grasset, Cindy Gutzeit, Mathieu Uzzan, Meera Ramanujam, Menno C van Zelm, Raquel Albero-González, Ivonne Vazquez, Mar Iglesias, Sergi Serrano, Lucía Márquez, Elena Mercade, Saurabh Mehandru, Andrea Cerutti
Secretory immunoglobulin A (SIgA) enhances host-microbiota symbiosis, whereas SIgM remains poorly understood. We found that gut IgM(+) plasma cells (PCs) were more abundant in humans than mice and clonally related to a large repertoire of memory IgM(+) B cells disseminated throughout the intestine but rare in systemic lymphoid organs. In addition to sharing a gut-specific gene signature with memory IgA(+) B cells, memory IgM(+) B cells were related to some IgA(+) clonotypes and switched to IgA in response to T cell-independent or T cell-dependent signals...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28709801/lymphatic-endothelial-cells-control-initiation-of-lymph-node-organogenesis
#18
Lucas Onder, Urs Mörbe, Natalia Pikor, Mario Novkovic, Hung-Wei Cheng, Thomas Hehlgans, Klaus Pfeffer, Burkhard Becher, Ari Waisman, Thomas Rülicke, Jennifer Gommerman, Christopher G Mueller, Shinichiro Sawa, Elke Scandella, Burkhard Ludewig
Lymph nodes (LNs) are strategically situated throughout the body at junctures of the blood vascular and lymphatic systems to direct immune responses against antigens draining from peripheral tissues. The current paradigm describes LN development as a programmed process that is governed through the interaction between mesenchymal lymphoid tissue organizer (LTo) cells and hematopoietic lymphoid tissue inducer (LTi) cells. Using cell-type-specific ablation of key molecules involved in lymphoid organogenesis, we found that initiation of LN development is dependent on LTi-cell-mediated activation of lymphatic endothelial cells (LECs) and that engagement of mesenchymal stromal cells is a succeeding event...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28666573/mlkl-the-protein-that-mediates-necroptosis-also-regulates-endosomal-trafficking-and-extracellular-vesicle-generation
#19
Seongmin Yoon, Andrew Kovalenko, Konstantin Bogdanov, David Wallach
Activation of the pseudokinase mixed lineage kinase domain-like (MLKL) upon its phosphorylation by the protein kinase RIPK3 triggers necroptosis, a form of programmed cell death in which rupture of cellular membranes yields release of intracellular components. We report that MLKL also associated with endosomes and controlled the transport of endocytosed proteins, thereby enhancing degradation of receptors and ligands, modulating their induced signaling and facilitating the generation of extracellular vesicles...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28636969/human-virus-derived-small-rnas-can-confer-antiviral-immunity-in-mammals
#20
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
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