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Immunity

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https://www.readbyqxmd.com/read/30217409/pip5-kinases-regulate-membrane-phosphoinositide-and-actin-composition-for-targeted-granule-secretion-by-cytotoxic-lymphocytes
#1
Christian M Gawden-Bone, Gordon L Frazer, Arianne C Richard, Claire Y Ma, Katharina Strege, Gillian M Griffiths
How cytotoxic T lymphocytes (CTLs) sense T cell receptor (TCR) signaling in order to specialize an area of plasma membrane for granule secretion is not understood. Here, we demonstrate that immune synapse formation led to rapid localized changes in the phosphoinositide composition of the plasma membrane, both reducing phosphoinositide-4-phosphate (PI(4)P), PI(4,5)P2, and PI(3,4,5)P3 and increasing diacylglycerol (DAG) and PI(3,4)P2 within the first 2 min of synapse formation. These changes reduced negative charge across the synapse, triggering the release of electrostatically bound PIP5 kinases that are required to replenish PI(4,5)P2...
September 8, 2018: Immunity
https://www.readbyqxmd.com/read/30193848/antibodies-set-boundaries-limiting-microbial-metabolite-penetration-and-the-resultant-mammalian-host-response
#2
Yasuhiro Uchimura, Tobias Fuhrer, Hai Li, Melissa A Lawson, Michael Zimmermann, Bahtiyar Yilmaz, Joel Zindel, Francesca Ronchi, Marcel Sorribas, Siegfried Hapfelmeier, Stephanie C Ganal-Vonarburg, Mercedes Gomez de Agüero, Kathy D McCoy, Uwe Sauer, Andrew J Macpherson
Although the mammalian microbiota is well contained within the intestine, it profoundly shapes development and metabolism of almost every host organ. We questioned the range and depth of microbial metabolite penetration into the host, and how this is modulated by intestinal immunity. Chemically identical microbial and host metabolites were distinguished by stable isotope tracing from 13 C-labeled live non-replicating Escherichia coli, differentiating 12 C host isotopes with high-resolution mass spectrometry...
August 31, 2018: Immunity
https://www.readbyqxmd.com/read/30193849/the-zinc-finger-protein-zcchc3-binds-rna-and-facilitates-viral-rna-sensing-and-activation-of-the-rig-i-like-receptors
#3
Huan Lian, Ru Zang, Jin Wei, Wen Ye, Ming-Ming Hu, Yun-Da Chen, Xia-Nan Zhang, Yi Guo, Cao-Qi Lei, Qing Yang, Wei-Wei Luo, Shu Li, Hong-Bing Shu
Recognition of viral RNA by the retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) initiates innate antiviral immune response. How the binding of viral RNA to and activation of the RLRs are regulated remains enigmatic. In this study, we identified ZCCHC3 as a positive regulator of the RLRs including RIG-I and MDA5. ZCCHC3 deficiency markedly inhibited RNA virus-triggered induction of downstream antiviral genes, and ZCCHC3-deficient mice were more susceptible to RNA virus infection. ZCCHC3 was associated with RIG-I and MDA5 and functions in two distinct processes for regulation of RIG-I and MDA5 activities...
August 27, 2018: Immunity
https://www.readbyqxmd.com/read/30170812/a-map-of-toll-like-receptor-expression-in-the-intestinal-epithelium-reveals-distinct-spatial-cell-type-specific-and-temporal-patterns
#4
April E Price, Kiarash Shamardani, Kyler A Lugo, Jacques Deguine, Allison W Roberts, Bettina L Lee, Gregory M Barton
Signaling by Toll-like receptors (TLRs) on intestinal epithelial cells (IECs) is critical for intestinal homeostasis. To visualize epithelial expression of individual TLRs in vivo, we generated five strains of reporter mice. These mice revealed that TLR expression varied dramatically along the length of the intestine. Indeed, small intestine (SI) IECs expressed low levels of multiple TLRs that were highly expressed by colonic IECs. TLR5 expression was restricted to Paneth cells in the SI epithelium. Intestinal organoid experiments revealed that TLR signaling in Paneth cells or colonic IECs induced a core set of host defense genes, but this set did not include antimicrobial peptides, which instead were induced indirectly by inflammatory cytokines...
August 27, 2018: Immunity
https://www.readbyqxmd.com/read/30170810/non-canonical-nf-%C3%AE%C2%BAb-antagonizes-sting-sensor-mediated-dna-sensing-in-radiotherapy
#5
Yuzhu Hou, Hua Liang, Enyu Rao, Wenxin Zheng, Xiaona Huang, Liufu Deng, Yuan Zhang, Xinshuang Yu, Meng Xu, Helena Mauceri, Ainhoa Arina, Ralph R Weichselbaum, Yang-Xin Fu
The NF-κB pathway plays a crucial role in supporting tumor initiation, progression, and radioresistance of tumor cells. However, the role of the NF-κB pathway in radiation-induced anti-tumor host immunity remains unclear. Here we demonstrated that inhibiting the canonical NF-κB pathway dampened the therapeutic effect of ionizing radiation (IR), whereas non-canonical NF-κB deficiency promoted IR-induced anti-tumor immunity. Mechanistic studies revealed that non-canonical NF-κB signaling in dendritic cells (DCs) was activated by the STING sensor-dependent DNA-sensing pathway...
August 17, 2018: Immunity
https://www.readbyqxmd.com/read/30170814/gasdermin-d-restrains-type-i-interferon-response-to-cytosolic-dna-by-disrupting-ionic-homeostasis
#6
Ishita Banerjee, Bharat Behl, Morena Mendonca, Gaurav Shrivastava, Ashley J Russo, Antoine Menoret, Arundhati Ghosh, Anthony T Vella, Sivapriya Kailasan Vanaja, Saumendra N Sarkar, Katherine A Fitzgerald, Vijay A K Rathinam
Inflammasome-activated caspase-1 cleaves gasdermin D to unmask its pore-forming activity, the predominant consequence of which is pyroptosis. Here, we report an additional biological role for gasdermin D in limiting cytosolic DNA surveillance. Cytosolic DNA is sensed by Aim2 and cyclic GMP-AMP synthase (cGAS) leading to inflammasome and type I interferon responses, respectively. We found that gasdermin D activated by the Aim2 inflammasome suppressed cGAS-driven type I interferon response to cytosolic DNA and Francisella novicida in macrophages...
August 14, 2018: Immunity
https://www.readbyqxmd.com/read/30170813/lung-%C3%AE-%C3%AE-t-cells-mediate-protective-responses-during-neonatal-influenza-infection-that-are-associated-with-type-2-immunity
#7
Xi-Zhi J Guo, Pradyot Dash, Jeremy Chase Crawford, E Kaitlynn Allen, Anthony E Zamora, David F Boyd, Susu Duan, Resha Bajracharya, Walid A Awad, Nopporn Apiwattanakul, Peter Vogel, Thirumala-Devi Kanneganti, Paul G Thomas
Compared to adults, infants suffer higher rates of hospitalization, severe clinical complications, and mortality due to influenza infection. We found that γδ T cells protected neonatal mice against mortality during influenza infection. γδ T cell deficiency did not alter viral clearance or interferon-γ production. Instead, neonatal influenza infection induced the accumulation of interleukin-17A (IL-17A)-producing γδ T cells, which was associated with IL-33 production by lung epithelial cells. Neonates lacking IL-17A-expressing γδ T cells or Il33 had higher mortality upon influenza infection...
August 14, 2018: Immunity
https://www.readbyqxmd.com/read/30231985/syk-card9-signaling-axis-promotes-gut-fungi-mediated-inflammasome-activation-to-restrict-colitis-and-colon-cancer
#8
Ankit Malik, Deepika Sharma, R K Subbarao Malireddi, Clifford S Guy, Ti-Cheng Chang, Scott R Olsen, Geoffrey Neale, Peter Vogel, Thirumala-Devi Kanneganti
Fungi represent a significant proportion of the gut microbiota. Aberrant immune responses to fungi are frequently observed in inflammatory bowel diseases (IBD) and colorectal cancer (CRC), and mutations in the fungal-sensing pathways are associated with the pathogenesis of IBD. Fungal recognition receptors trigger downstream signaling via the common adaptor protein CARD9 and the kinase SYK. Here we found that commensal gut fungi promoted inflammasome activation during AOM-DSS-induced colitis. Myeloid cell-specific deletion of Card9 or Syk reduced inflammasome activation and interleukin (IL)-18 maturation and increased susceptibility to colitis and CRC...
September 18, 2018: Immunity
https://www.readbyqxmd.com/read/30231984/the-adaptor-protein-card9-protects-against-colon-cancer-by-restricting-mycobiota-mediated-expansion-of-myeloid-derived-suppressor-cells
#9
Tingting Wang, Chaogang Fan, Anran Yao, Xingwei Xu, Guoxing Zheng, Yun You, Changying Jiang, Xueqiang Zhao, Yayi Hou, Mien-Chie Hung, Xin Lin
The adaptor protein CARD9 links detection of fungi by surface receptors to the activation of the NF-κB pathway. Mice deficient in CARD9 exhibit dysbiosis and are more susceptible to colitis. Here we examined the impact of Card9 deficiency in the development of colitis-associated colon cancer (CAC). Treatment of Card9-/- mice with AOM-DSS resulted in increased tumor loads as compared to WT mice and in the accumulation of myeloid-derived suppressor cells (MDSCs) in tumor tissue. The impaired fungicidal functions of Card9-/- macrophages led to increased fungal loads and variation in the overall composition of the intestinal mycobiota, with a notable increase in C...
September 18, 2018: Immunity
https://www.readbyqxmd.com/read/30231983/germinal-center-b-cells-replace-their-antigen-receptors-in-dark-zones-and-fail-light-zone-entry-when-immunoglobulin-gene-mutations-are-damaging
#10
Isabelle Stewart, Daniel Radtke, Bethan Phillips, Simon J McGowan, Oliver Bannard
Adaptive immunity involves the development of bespoke antibodies in germinal centers (GCs) through immunoglobulin somatic hypermutation (SHM) in GC dark zones (DZs) and clonal selection in light zones (LZs). Accurate selection requires that cells fully replace surface B cell receptors (BCRs) following SHM, but whether this happens before LZ entry is not clear. We found that most GC B cells degrade pre-SHM receptors before leaving the DZ, and that B cells acquiring crippling mutations during SHM rarely reached the LZ...
September 18, 2018: Immunity
https://www.readbyqxmd.com/read/30231982/interferons-and-proinflammatory-cytokines-in-pregnancy-and-fetal-development
#11
REVIEW
Laura J Yockey, Akiko Iwasaki
Successful pregnancy requires carefully-coordinated communications between the mother and fetus. Immune cells and cytokine signaling pathways participate as mediators of these communications to promote healthy pregnancy. At the same time, certain infections or inflammatory conditions in pregnant mothers cause severe disease and have detrimental impacts on the developing fetus. In this review, we examine evidence for the role of maternal and fetal immune responses affecting pregnancy and fetal development, both under homeostasis and following infection...
September 18, 2018: Immunity
https://www.readbyqxmd.com/read/30231981/tissue-crosstalk-in-t1d-is-insulin-special
#12
Braxton L Jamison, Kathryn Haskins
In a recent issue of Nature,Wan et al. (2018) show that glucose-stimulated β cells secrete insulin B chain peptides relevant to autoimmunity in type 1 diabetes. Peptides such as insulin B:12-20 are released into circulation, where they can be directly and broadly presented by antigen-presenting cells throughout the lymphatic system.
September 18, 2018: Immunity
https://www.readbyqxmd.com/read/30231980/viral-anti-crispr-tactics-no-success-without-sacrifice
#13
Michiel van Gent, Michaela U Gack
Co-evolution with their bacterial hosts has led to viral countermeasures against CRISPR-mediated immunity. In a recent issue of Cell, Landsberger et al. (2018) and Borges et al. (2018) report that cooperation among bacteriophages and multiple infection events are necessary to overcome CRISPR immune responses.
September 18, 2018: Immunity
https://www.readbyqxmd.com/read/30231979/identifying-the-patterns-of-pattern-recognition-receptors
#14
Andrea A Hill, Gretchen E Diehl
Intestinal homeostasis requires microbial recognition that results in appropriate responses to commensals and pathogens. In this issue of Immunity, Price et al. (2018) map the in vivo expression of five toll-like receptors (TLR) in intestinal epithelia, revealing distinct spatio-temporal expression patterns that shape responses to TLR ligands.
September 18, 2018: Immunity
https://www.readbyqxmd.com/read/30231978/gone-with-the-antibody
#15
Silvia Guglietta, Maria Rescigno
Bacterial metabolites can reach distant organs, and in this issue of Immunity, Uchimura et al. (2018) show a fast systemic distribution of microbiota metabolites. This distribution is controlled by antibodies that accelerate bacterial transit through the small intestine, resulting in reduced local and systemic metabolite penetration and attenuation of immune responses.
September 18, 2018: Immunity
https://www.readbyqxmd.com/read/30231977/fungi-enter-the-stage-of-colon-carcinogenesis
#16
Claire Conche, Florian R Greten
The significant contribution of intestinal bacteria for the pathogenesis of colorectal cancer is widely accepted by now. In this issue of Immunity, two articles by Malik et al. (2018) and Wang et al. (2018) highlight the role of commensal fungi, which so far have been underestimated.
September 18, 2018: Immunity
https://www.readbyqxmd.com/read/30231976/two-factor-authentication-for-type-2-immunity
#17
Jennifer S Chen, Stephanie C Eisenbarth
The initiation of type 2 responses is tightly regulated. In this issue of Immunity, Sokol et al. (2018) demonstrate that CCL8 is a critical signal that licenses dendritic cells to enter the lymph node parenchyma and induce Th2 differentiation after allergen exposure.
September 18, 2018: Immunity
https://www.readbyqxmd.com/read/30231975/ion-man-gsdmd-punches-pores-to-knock-out-cgas
#18
Rebecca Feltham, James E Vince
The pore-forming protein GSDMD promotes cytokine release and induces pyroptotic cell death. In this issue of Immunity, Banerjee et al. (2018) document how GSDMD triggers potassium efflux to inhibit cGAS-STING and prevent damaging interferon production after bacterial infection.
September 18, 2018: Immunity
https://www.readbyqxmd.com/read/30231974/immunity-in-the-very-young-challenges-and-opportunities
#19
(no author information available yet)
Immunity in early life encompasses the delicate interphase at the maternal-fetal stage, as well as rapid development and adaptation that occur as the newborn transitions from the protected maternal environment to functioning in the outside world. Understanding the forces that shape immunity in the very young and that lay the groundwork for an effective adult immune system holds both questions and promise.
September 18, 2018: Immunity
https://www.readbyqxmd.com/read/30193847/cd56-expression-marks-human-group-2-innate-lymphoid-cell-divergence-from-a-shared-nk-cell-and-group-3-innate-lymphoid-cell-developmental-pathway
#20
Luxi Chen, Youssef Youssef, Cameron Robinson, Gabrielle F Ernst, Mary Y Carson, Karen A Young, Steven D Scoville, Xiaoli Zhang, Regine Harris, Palak Sekhri, Anthony G Mansour, Wing K Chan, Ansel P Nalin, Hsiaoyin C Mao, Tiffany Hughes, Emily M Mace, Yinghong Pan, Navin Rustagi, Sujash S Chatterjee, Preethi H Gunaratne, Gregory K Behbehani, Bethany L Mundy-Bosse, Michael A Caligiuri, Aharon G Freud
According to the established model of murine innate lymphoid cell (ILC) development, helper ILCs develop separately from natural killer (NK) cells. However, it is unclear how helper ILCs and NK cells develop in humans. Here we elucidated key steps of NK cell, ILC2, and ILC3 development within human tonsils using ex vivo molecular and functional profiling and lineage differentiation assays. We demonstrated that while tonsillar NK cells, ILC2s, and ILC3s originated from a common CD34- CD117+ ILC precursor pool, final steps of ILC2 development deviated independently and became mutually exclusive from those of NK cells and ILC3s, whose developmental pathways overlapped...
September 18, 2018: Immunity
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