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Immunity

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https://www.readbyqxmd.com/read/28801233/t-cell-zone-resident-macrophages-silently-dispose-of-apoptotic-cells-in-the-lymph-node
#1
Myriam Baratin, Léa Simon, Audrey Jorquera, Clément Ghigo, Doulaye Dembele, Jonathan Nowak, Rebecca Gentek, Stephan Wienert, Frederick Klauschen, Bernard Malissen, Marc Dalod, Marc Bajénoff
In lymph nodes (LNs), dendritic cells (DCs) are thought to dispose of apoptotic cells, a function pertaining to macrophages in other tissues. We found that a population of CX3CR1(+) MERTK(+) cells located in the T cell zone of LNs, previously identified as DCs, are efferocytic macrophages. Lineage-tracing experiments and shield chimeras indicated that these T zone macrophages (TZM) are long-lived macrophages seeded in utero and slowly replaced by blood monocytes after birth. Imaging the LNs of mice in which TZM and DCs express different fluorescent proteins revealed that TZM-and not DCs-act as the only professional scavengers, clearing apoptotic cells in the LN T cell zone in a CX3CR1-dependent manner...
August 4, 2017: Immunity
https://www.readbyqxmd.com/read/28801231/anti-inflammatory-chromatinscape-suggests-alternative-mechanisms-of-glucocorticoid-receptor-action
#2
Kyu-Seon Oh, Heta Patel, Rachel A Gottschalk, Wai Shing Lee, Songjoon Baek, Iain D C Fraser, Gordon L Hager, Myong-Hee Sung
Despite the widespread use of glucocorticoids (GCs), their anti-inflammatory effects are not understood mechanistically. Numerous investigations have examined the effects of glucocorticoid receptor (GR) activation prior to inflammatory challenges. However, clinical situations are emulated by a GC intervention initiated in the midst of rampant inflammatory responses. To characterize the effects of a late GC treatment, we profiled macrophage transcriptional and chromatinscapes with Dexamethasone (Dex) treatment before or after stimulation by lipopolysaccharide (LPS)...
August 4, 2017: Immunity
https://www.readbyqxmd.com/read/28801234/dendritic-cells-but-not-macrophages-sense-tumor-mitochondrial-dna-for-cross-priming-through-signal-regulatory-protein-%C3%AE-signaling
#3
Meng Michelle Xu, Yang Pu, Dali Han, Yaoyao Shi, Xuezhi Cao, Hua Liang, Xiang Chen, Xiao-Dong Li, Liufu Deng, Zhijian J Chen, Ralph R Weichselbaum, Yang-Xin Fu
Inhibition of cytosolic DNA sensing represents a strategy that tumor cells use for immune evasion, but the underlying mechanisms are unclear. Here we have shown that CD47-signal regulatory protein α (SIRPα) axis dictates the fate of ingested DNA in DCs for immune evasion. Although macrophages were more potent in uptaking tumor DNA, increase of DNA sensing by blocking the interaction of SIRPα with CD47 preferentially occurred in dendritic cells (DCs) but not in macrophages. Mechanistically, CD47 blockade enabled the activation of NADPH oxidase NOX2 in DCs, which in turn inhibited phagosomal acidification and reduced the degradation of tumor mitochondrial DNA (mtDNA) in DCs...
August 2, 2017: Immunity
https://www.readbyqxmd.com/read/28801232/nlrp6-and-asc-dependent-inflammasomes-do-not-shape-the-commensal-gut-microbiota-composition
#4
Michail Mamantopoulos, Francesca Ronchi, Filip Van Hauwermeiren, Sara Vieira-Silva, Bahtiyar Yilmaz, Liesbet Martens, Yvan Saeys, Stefan K Drexler, Amir S Yazdi, Jeroen Raes, Mohamed Lamkanfi, Kathy D McCoy, Andy Wullaert
The gut microbiota regulate susceptibility to multiple human diseases. The Nlrp6-ASC inflammasome is widely regarded as a hallmark host innate immune axis that shapes the gut microbiota composition. This notion stems from studies reporting dysbiosis in mice lacking these inflammasome components when compared with non-littermate wild-type animals. Here, we describe microbial analyses in inflammasome-deficient mice while minimizing non-genetic confounders using littermate-controlled Nlrp6-deficient mice and ex-germ-free littermate-controlled ASC-deficient mice that were all allowed to shape their gut microbiota naturally after birth...
August 2, 2017: Immunity
https://www.readbyqxmd.com/read/28778586/analyses-of-a-mutant-foxp3-allele-reveal-batf-as-a-critical-transcription-factor-in-the-differentiation-and-accumulation-of-tissue-regulatory-t-cells
#5
Norihito Hayatsu, Takahisa Miyao, Masashi Tachibana, Ryuichi Murakami, Akihiko Kimura, Takako Kato, Eiryo Kawakami, Takaho A Endo, Ruka Setoguchi, Hiroshi Watarai, Takeshi Nishikawa, Takuwa Yasuda, Hisahiro Yoshida, Shohei Hori
Foxp3 controls the development and function of regulatory T (Treg) cells, but it remains elusive how Foxp3 functions in vivo. Here, we established mouse models harboring three unique missense Foxp3 mutations that were identified in patients with the autoimmune disease IPEX. The I363V and R397W mutations were loss-of-function mutations, causing multi-organ inflammation by globally compromising Treg cell physiology. By contrast, the A384T mutation induced a distinctive tissue-restricted inflammation by specifically impairing the ability of Treg cells to compete with pathogenic T cells in certain non-lymphoid tissues...
July 28, 2017: Immunity
https://www.readbyqxmd.com/read/28723556/peroxisome-mediated-metabolism-is-required-for-immune-response-to-microbial-infection
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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