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| Open AccessAdjuvant-dependent impact of inactivated SARS-CoV-2 vaccines during heterologous infection by a SARS-related coronavirus
Here, Dillard and Taft-Benz et al. show in a female mouse model how different adjuvants affect inactivated vaccine-mediated protection against homologous SARS-CoV-2 and heterologous SARS-CoV-1-like coronaviruses. They find that an aluminum hydroxide-adjuvanted vaccine can increase risk of adverse outcomes during heterologous infection.
- Jacob A. Dillard
- , Sharon A. Taft-Benz
- & Mark T. Heise
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Article
| Open AccessDiscovery of immunotherapy targets for pediatric solid and brain tumors by exon-level expression
CAR T cell immunotherapy for paediatric solid and brain tumours is constrained by the availability of targetable antigens. Here, the authors investigate the landscape of cancer-specific exons as potential targets by analysing 1,532 RNAseq datasets from 16 types of paediatric solid and brain tumours.
- Timothy I. Shaw
- , Jessica Wagner
- & Stephen Gottschalk
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Article
| Open AccessCD74 supports accumulation and function of regulatory T cells in tumors
CD74, the MHC class II invariant chain, was thought to be mainly expressed by antigen presenting cells. Here the authors report that CD74 is overexpressed by human tumor infiltrating regulatory T cells (Tregs) and that its loss affects Treg accumulation and function in tumors.
- Elisa Bonnin
- , Maria Rodrigo Riestra
- & Eliane Piaggio
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Article
| Open AccessAnnoSpat annotates cell types and quantifies cellular arrangements from spatial proteomics
Annotation of cell types and quantification of their relative localization in tissues remain challenging. Here, the authors present AnnoSpat (Annotator and Spatial Pattern Finder), a computational tool that can automatically identify cell types and quantify cell-cell proximity relationships.
- Aanchal Mongia
- , Fatema Tuz Zohora
- & Robert B. Faryabi
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Article
| Open AccessAirway epithelial CD47 plays a critical role in inducing influenza virus-mediated bacterial super-infection
During the influenza pandemic, a large number of deaths resulted from secondary bacterial pneumonia caused by common upper respiratory tract bacteria, such as Staphylococcus. Here, Moon et al, find that the interaction between airway epithelial CD47 and the pathogenic bacterial FnBP is critical in causing bacterial superinfection.
- Sungmin Moon
- , Seunghan Han
- & Ji-Hwan Ryu
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Article
| Open AccessGenomic deletion of Bcl6 differentially affects conventional dendritic cell subsets and compromises Tfh/Tfr/Th17 cell responses
Conventional dendritic cells are playing a pivotal role at the interface of innate and adaptive immunity, but they are a heterogenous group regarding function and regulation. Here, the authors show that although Bcl6-deficiency does not regulate general DC subset identity, Bcl6 expression is required for a specific subset of type 2 DCs in mice, resulting in impaired T helper cell responses and further clarifying molecular players driving DC subset heterogeneity.
- Hongkui Xiao
- , Isabel Ulmert
- & Katharina Lahl
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Article
| Open AccessPrimary prophylaxis with mTOR inhibitor enhances T cell effector function and prevents heart transplant rejection during talimogene laherparepvec therapy of squamous cell carcinoma
Cutaneous squamous cell carcinoma is more frequent and more aggressive in the organ transplanted and represent a therapeutic challenge due to the ongoing transplantrelated immune suppression. Here, the authors present a case report of a patient whose T cell responses were successfully strengthened via primary prophylactic therapy with mammalian target of rapamycin inhibition and intra-lesion injection of the oncolytic herpesvirus T-VEC.
- Victor Joo
- , Karim Abdelhamid
- & Michel Obeid
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Article
| Open AccessCD8+ T-cell responses towards conserved influenza B virus epitopes across anatomical sites and age
Influenza B viruses are linked to significant morbidity and mortality, and yet their immunobiology is comparatively poorly understood. Here Menon et al identify influenza B virus-specific CD8+ T cell epitopes and characterise these in adults, children and the elderly.
- Tejas Menon
- , Patricia T. Illing
- & Katherine Kedzierska
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Article
| Open AccessAntigen presentation plays positive roles in the regenerative response to cardiac injury in zebrafish
An adequate immune response is necessary to promote heart regeneration. Here, the authors identified a link between antigen presentation, immune cells, and endocardial cells during the regenerative response to cardiac injury in the adult zebrafish.
- João Cardeira-da-Silva
- , Qianchen Wang
- & Didier Y. R. Stainier
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Article
| Open AccessThe hinge-engineered IgG1-IgG3 hybrid subclass IgGh47 potently enhances Fc-mediated function of anti-streptococcal and SARS-CoV-2 antibodies
Here, the authors elongated the hinge structure of IgG1 monoclonal antibodies. The modified IgG1-IgG3 hybrid subclass showed enhanced Fc-mediated function compared to IgG1 in two distinct biological systems, Streptococcus pyogenes and SARS-CoV-2.
- Arman Izadi
- , Yasaman Karami
- & Pontus Nordenfelt
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Article
| Open AccessOxygen enhances antiviral innate immunity through maintenance of EGLN1-catalyzed proline hydroxylation of IRF3
Oxygen is an essential requirement for aerobic organisms. Here the authors explore the role of oxygen in the antiviral innate response in multiple models of infection and suggest oxygen enhances the antiviral innate response via EGLN1 hydroxylation of IRF3.
- Xing Liu
- , Jinhua Tang
- & Wuhan Xiao
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Article
| Open AccessCAR affinity modulates the sensitivity of CAR-T cells to PD-1/PD-L1-mediated inhibition
It has been suggested that targeting the PD-1/PD-L1 axis can increase the anti-tumor properties of chimeric antigen receptor (CAR)-T cells. Here the authors report that CAR affinity modulates the sensitivity of CAR-T cells to PD-1/PD-L1-mediated inhibition.
- Irene Andreu-Saumell
- , Alba Rodriguez-Garcia
- & Sonia Guedan
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Article
| Open AccessMucosal prime-boost immunization with live murine pneumonia virus-vectored SARS-CoV-2 vaccine is protective in macaques
Immunization via the respiratory route is predicted to increase the effectiveness of SARS-CoV-2 vaccines. Here, Kaiser et al. describe a murine pneumonia virus vectored vaccine expressing spike protein, and show that intranasal immunization of male rhesus macaques provides good mucosal and systemic immunogenicity and efficacy.
- Jaclyn A. Kaiser
- , Christine E. Nelson
- & Cyril Le Nouën
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Article
| Open AccessThe gut commensal Blautia maintains colonic mucus function under low-fiber consumption through secretion of short-chain fatty acids
Here, the authors show that elevating fiber intake in humans alters their gut microbiota, which, upon transplantation into mice, enhances intestinal mucus function, and identify a crucial role played by the commensal bacterium Blautia and its fermentation products.
- Sandra M. Holmberg
- , Rachel H. Feeney
- & Bjoern O. Schroeder
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Article
| Open AccessA comprehensive synthetic library of poly-N-acetyl glucosamines enabled vaccine against lethal challenges of Staphylococcus aureus
Poly-β-(1–6)-N-acetylglucosamine (PNAG) is an important vaccine target, but the impact of the number and position of free amine vs N-acetylation on its antigenicity is not well understood. Here, the authors report a divergent strategy to synthesize a comprehensive library of PNAG pentasaccharides, enabling the identification of enhanced epitopes for vaccines against Staphylococcus aureus including drug resistant strains.
- Zibin Tan
- , Weizhun Yang
- & Xuefei Huang
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Article
| Open AccessPD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupus
Basophils have been implicated in systemic lupus erythematosus (SLE), as evidenced by the fact that basophil-deficient mice do not develop the disease. Here, the authors demonstrate that PD-L1 and IL-4 expression in basophils promotes the pathogenic accumulation of follicular helper T cells in patients with SLE and murine models.
- John TCHEN
- , Quentin SIMON
- & Nicolas CHARLES
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Article
| Open AccessLSD1 drives intestinal epithelial maturation and controls small intestinal immune cell composition independent of microbiota in a murine model
Post birth the gastrointestinal tract undergoes development including the establishment of the microbiome, establishment of tolerance and maturation of the epithelium. Here the authors show a histone demethylase LSD1 is required for postnatal intestinal epithelium maturation and how this impacts local immune cell composition and gut homeostasis.
- Alberto Díez-Sánchez
- , Håvard T. Lindholm
- & Menno J. Oudhoff
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Article
| Open AccessAn ancestral SARS-CoV-2 vaccine induces anti-Omicron variants antibodies by hypermutation
Repeat vaccination with COVID-19 mRNA vaccines has been shown to increase breadth of the antibody response. Here the authors demonstrate that B cell clones induced by the ancestral COVID-19 vaccine develop into daughter clones with different reactivity to individual SARS-CoV-2 variants through the accumulation of somatic hypermutations.
- Seoryeong Park
- , Jaewon Choi
- & Junho Chung
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Article
| Open AccessAn esophagus cell atlas reveals dynamic rewiring during active eosinophilic esophagitis and remission
Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus with unclear immune cell involvement. Here the authors generate a single cell transcriptomic dataset with 400k cells from the esophageal mucosa of active EoE patients, remission EoE patients, and healthy individuals to characterise esophageal cellular composition, phenotype and interaction in this disease.
- Jiarui Ding
- , John J. Garber
- & Ramnik J. Xavier
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Article
| Open AccessConsistent survival in consecutive cases of life-supporting porcine kidney xenotransplantation using 10GE source pigs
Xenotransplantation is an imminent clinical reality but concerns remain around the logistics of procurement and the experimental immunosuppression regimens required to achieve long-term xenograft survival. Here the authors show more than 6 month survival of genetically modified porcine kidneys in baboons after regulatory compliant organ procurements, clinically relevant organ preservation times and FDA-approved immunosuppressive reagents.
- Daniel Eisenson
- , Yu Hisadome
- & Kazuhiko Yamada
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Article
| Open AccessAntiviral cellular therapy for enhancing T-cell reconstitution before or after hematopoietic stem cell transplantation (ACES): a two-arm, open label phase II interventional trial of pediatric patients with risk factor assessment
Viral infection is a common risk for immune-compromised individuals, particularly pediatric patients receiving hematopoietic stem cell transplants. Here the authors report a phase II trial testing adoptive transfer of third party, virus-specific T cells on the feasibility, safety, clinical responses, as well as homeostasis of antiviral immunity in the recipients.
- Michael D. Keller
- , Patrick J. Hanley
- & Michael A. Pulsipher
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Article
| Open AccessImpact of PEG sensitization on the efficacy of PEG hydrogel-mediated tissue engineering
Concerns over the immunogenicity of poly(ethylene glycol) (PEG) are growing, and the implications for tissue engineering are unknown. Here the authors evaluate the impact of anti-PEG antibodies and PEG immunogenicity on the efficacy of a PEG hydrogel-based tissue engineering therapy.
- Alisa H. Isaac
- , Sarea Y. Recalde Phillips
- & Daniel L. Alge
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Article
| Open AccessInflammation and cytomegalovirus viremia during pregnancy drive sex-differentiated differences in mortality and immune development in HIV-exposed infants
HIV exposed but uninfected infants may face an increased risk of serious infection and mortality. In this work, the authors utilise a cohort from rural Zimbabwe to explore the biological mechanisms underlying infant mortality.
- Ceri Evans
- , Kuda Mutasa
- & Andrew J. Prendergast
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Article
| Open AccessImprovement of immune dysregulation in individuals with long COVID at 24-months following SARS-CoV-2 infection
Post-acute sequelae of COVID (PASC) or long-COVID can affect a proportion of those infected but this is not well understood. Here the authors perform a single cell transcriptomics analysis of immune cells from long-COVID patients at 24 months and find that cell changes observed at 3 and 8 months do not persist to 24 months.
- Chansavath Phetsouphanh
- , Brendan Jacka
- & Gail V. Matthews
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Article
| Open AccessEmerging variants develop total escape from potent monoclonal antibodies induced by BA.4/5 infection
Many emerging SARS-CoV-2 variants partially escape the humoral immune response. Here, Liu et al. characterize 28 antibodies from BA.4/5 breakthrough infections and find attrition of neutralization and complete loss of function for variants with Spike mutations at positions 455 and 456.
- Chang Liu
- , Raksha Das
- & Gavin R. Screaton
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Article
| Open AccessCXCL5 activates CXCR2 in nociceptive sensory neurons to drive joint pain and inflammation in experimental gouty arthritis
Here, the authors demonstrate that CXCL5 expression is increased in ankle joints of gouty arthritis model mice. CXCL5-neuronal CXCR2-TRPA1 axis contributes to gouty arthritis pain, neutrophil influx and joint inflammation.
- Chengyu Yin
- , Boyu Liu
- & Boyi Liu
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Article
| Open AccessDonor regulatory T cells rapidly adapt to recipient tissues to control murine acute graft-versus-host disease
Graft-versus-Host disease is a major complication after allogeneic bone marrow transplantation and is ameliorated by adoptively transferred donor regulatory T cells. Here, the authors apply transcriptomic and TCR profiling to assess regulatory T cell organ-specific adaptation in murine bone marrow transplantation models.
- David J. Dittmar
- , Franziska Pielmeier
- & Michael Rehli
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Article
| Open AccessDeep learning predictions of TCR-epitope interactions reveal epitope-specific chains in dual alpha T cells
Prediction of the specificity of a T cell receptor from amino acid sequence has been performed using different methods and approaches. Here the authors use TCRab sequences with known specificity to develop a deep learning TCR-epitope interaction predictor and use this method to predict specificity of dual alpha chain TCRs and TCRs specific for different antigens.
- Giancarlo Croce
- , Sara Bobisse
- & David Gfeller
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Article
| Open AccessInfluenza antibody breadth and effector functions are immune correlates from acquisition of pandemic infection of children
In this study, the authors assessed influenza-specific antibody responses in a cohort of seasonally vaccinated children and report that seasonal vaccination is beneficial by enhancing pandemic influenza virus-specific antibodies and cross-reactive effector functions.
- Janice Z. Jia
- , Carolyn A. Cohen
- & Sophie A. Valkenburg
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Article
| Open AccessA plant NLR receptor employs ABA central regulator PP2C-SnRK2 to activate antiviral immunity
Huang et al. show how plant Sw-5b NLR mimics the ABA receptor to activate ABA-dependent antiviral immunity via the PP2C-SnRK2 complex. They reveal that Sw-5b NLR induces ABA accumulation, upregulates ABA response genes, and triggers defense against viral infections by releasing SnRK2 from PP2C inhibition.
- Shen Huang
- , Chunli Wang
- & Xiaorong Tao
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Article
| Open AccessSemaphorin 3A causes immune suppression by inducing cytoskeletal paralysis in tumour-specific CD8+ T cells
Interactions between Semaphorin-3A (SEMA3A) and Neuropilin-1 (NRP1) and Plexin-A1 and Plexin-A4 have been shown to affect T cell development. Here the authors investigate how these interactions affect CD8+ T cells in tumour immunity, showing that NRP-1, Plexin-A1 and Plexin-A4 are upregulated on T cells allowing tumour derived SEMA3A to inhibit CD8+ T cell migration and function.
- Mike B. Barnkob
- , Yale S. Michaels
- & Vincenzo Cerundolo
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Article
| Open AccessSystematic investigation of chemo-immunotherapy synergism to shift anti-PD-1 resistance in cancer
The design of new combinatorial regimens represents an opportunity to improve response to immune checkpoint inhibitors in patients with cancer. Here the authors computationally model the interaction between chemotherapy and immunotherapy by studying treatment-induced expression changes associated with response to anti-PD-1, identifying chemotherapeutic drugs or small molecule inhibitors that can overcome resistance to anti-PD-1.
- Yue Wang
- , Dhamotharan Pattarayan
- & Da Yang
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Article
| Open AccessSpatiotemporal immune atlas of a clinical-grade gene-edited pig-to-human kidney xenotransplant
Xenotransplantation in humans using pig organs could improve the transplant organ supply. Here the authors transplant pig kidneys into a brain-dead recipient and monitor the human immune cell response early after transplantation using spatial and single cell transcriptomics and show early myeloid cell infiltration.
- Matthew D. Cheung
- , Rebecca Asiimwe
- & Paige M. Porrett
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Article
| Open AccessCoPoP liposomes displaying stabilized clade C HIV-1 Env elicit tier 2 multiclade neutralization in rabbits
HIV vaccine candidates often have limited capacity to induce broadly neutralizing antibodies (nAbs). In this study, the authors show that stabilized Clade C HIV-1 Env protein trimers decorated on CoPoP liposomes induce nAbs against 18 of 20 multiclade tier 2 HIV-1 strains in immunized rabbits.
- Annemart Koornneef
- , Kanika Vanshylla
- & Frank Wegmann
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Article
| Open AccessEvolution of T cells in the cancer-resistant naked mole-rat
Naked mole-rats are long-lived rodents with remarkable resistance to cancer. Here authors show that their T-cell compartment is different from that of mice in that they have a large population of circulating cytotoxic γδ T cells harboring a dominant clonotype, and the clonotypic diversity of their conventional cytotoxic αβ T cells is more modest than that of mice.
- Tzuhua D. Lin
- , Nimrod D. Rubinstein
- & Rochelle Buffenstein
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Article
| Open AccessEarly-life exercise induces immunometabolic epigenetic modification enhancing anti-inflammatory immunity in middle-aged male mice
Exercise could affect the immune system, but whether early-life exercise could benefit immune health in adulthood is not fully understood. Here the authors show that early-life exercise promotes epi-metabolic changes in the liver to potentially benefit immunity in older age and characterise the involvement of pipecolic acid in this process.
- Nini Zhang
- , Xinpei Wang
- & Feng Gao
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Article
| Open AccessVaccination impairs de novo immune response to omicron breakthrough infection, a precondition for the original antigenic sin
Immune imprinting can affect the response to future infection with pathogen variants. Here, Pušnik et. al. demonstrate that previous vaccination with wild-type SARS-CoV-2 vaccine hampers the formation of an immune response to mutated regions of omicron surface proteins following omicron breakthrough infection.
- Jernej Pušnik
- , Jasmin Zorn
- & Hendrik Streeck
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Article
| Open AccessImmunoglobulin G N-glycan markers of accelerated biological aging during chronic HIV infection
In this study, Giron et al. find that people living with chronic HIV experience accelerated aging-associated alterations in antibody glycans. These alterations, attributed to senescence enzymes, predict comorbidities and reduce the antiviral function of antibodies.
- Leila B. Giron
- , Qin Liu
- & Mohamed Abdel-Mohsen
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Article
| Open AccessAntigen-specific Fab profiling achieves molecular-resolution analysis of human autoantibody repertoires in rheumatoid arthritis
Although many autoimmune diseases are characterized by the presence of autoantibodies, complete characterisation of autoantibody repertoires is lacking. Here, the authors introduce an autoantigen-specific Fab profiling method to show that the autoantibody repertoire in rheumatoid arthritis is diverse yet dominated only by a few clones.
- Eva Maria Stork
- , Danique M. H. van Rijswijck
- & Albert Bondt
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Article
| Open AccessSARS-CoV-2-specific cellular and humoral immunity after bivalent BA.4/5 COVID-19-vaccination in previously infected and non-infected individuals
Prior infection or exposure to SARS-CoV-2 may influence immunogenicity and effectiveness of subsequent vaccination to new strains of virus. Here the authors show that immunogenicity of a BA.4/5 mRNA vaccine differed in recipients depending on whether they had been exposed to or infected with an earlier strain of virus.
- Rebecca Urschel
- , Saskia Bronder
- & Martina Sester
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Article
| Open AccessDHX9 maintains epithelial homeostasis by restraining R-loop-mediated genomic instability in intestinal stem cells
Inflammatory bowel disease (IBD) is featured with epithelial barrier dysfunction, however, the underlying mechanism is less clear. Here, the authors show that DHX9 deficiency in intestinal stem cells (ISCs) induces accumulation of abnormal R-loops and subsequent genomic instability, leading to impairment of ISCs and development of IBD.
- Xingxing Ren
- , Qiuyuan Liu
- & Shu Zhu
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Article
| Open AccessDermal injury drives a skin to gut axis that disrupts the intestinal microbiome and intestinal immune homeostasis in mice
The microbial community in the intestine can affect other organs such as the skin but it is not clear if the opposite can occur. Here the authors show that skin wounding affects the microbial composition of the intestinal flora which then enhances DSS induced colitis and intestinal inflammation.
- Tatsuya Dokoshi
- , Yang Chen
- & Richard L. Gallo
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Article
| Open AccessA live attenuated vaccine to prevent severe neonatal Escherichia coli K1 infections
Authors utilise a murine model of Escherichia coli infection to immunologically characterise the properties of their live attenuated vaccine candidate. They also demonstrate protection of newborn mice following maternal immunisation.
- Youssouf Sereme
- , Cécile Schrimp
- & David Skurnik
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Article
| Open AccessExtracellular DNA traps in a ctenophore demonstrate immune cell behaviors in a non-bilaterian
Identifying core mechanisms of immune cells is critical for understanding the evolution of animal immune function. Here, Vandepas et al. report that ctenophore immune-like cells release extracellular DNA traps when exposed to microbes.
- Lauren E. Vandepas
- , Caroline Stefani
- & Adam Lacy-Hulbert
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Article
| Open AccessPhage-specific immunity impairs efficacy of bacteriophage targeting Vancomycin Resistant Enterococcus in a murine model
Bacteriophage can be used to target bacterial infection and used as a therapeutic approach for antibiotic resistant bacteria. Here the authors show that the use of bacteriophage to target antibiotic resistant bacteria in a mouse model of infection can induce phage specific immune responses and may impair their therapeutic efficacy.
- Julia D. Berkson
- , Claire E. Wate
- & Paul E. Carlson Jr.
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Article
| Open AccessPotent human neutralizing antibodies against Nipah virus derived from two ancestral antibody heavy chains
Nipah virus is a WHO priority pathogen, and there is currently no approved drug for clinical therapy. Here, the authors identified potent human neutralizing antibodies that block receptor binding and provide protection against NiV infection in vivo.
- Li Chen
- , Mengmeng Sun
- & Sandra Chiu
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Article
| Open AccessSenescent-like macrophages mediate angiogenesis for endplate sclerosis via IL-10 secretion in male mice
In their previous study, the researchers systematically revealed that endplate sclerosis is a significant aspect of spine degeneration or aging and a primary source of spinal pain. However, the underlying mechanisms of endplate sclerosis remained unclear. In their current report, it is shown that senescent cells accumulate in the sclerotic endplates of lumbar spine instability (LSI) or aging mouse models. The clearance of these senescent cells was found to restrain angiogenesis coupled with endplate sclerosis. Notably, macrophages were identified as undergoing senescence in the sclerotic endplates. The specific knockout of cdkn2a (p16) in macrophages abrogated LSI or aging-induced angiogenesis and sclerosis in the endplates. Moreover, both in vivo and in vitro studies indicated that IL-10 mediates the effects of senescent macrophages on angiogenesis and sclerosis in the endplates. Overall, these findings suggest that senescent macrophages orchestrate angiogenesis coupling with endplate sclerosis via the IL-10/pSTAT3 axis. This study enhances the understanding of the connection between immune senescence and endplate sclerosis and uncovers senescent macrophage-initiated endplate sclerosis as potential therapeutic targets for spinal degeneration.
- Yonggang Fan
- , Weixin Zhang
- & Shuangfei Ni
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Article
| Open AccessDevelopmental self-reactivity determines pathogenic Tc17 differentiation potential of naive CD8+ T cells in murine models of inflammation
The heterogeneity in naive CD8+ T cells is essential for diverse immune responses. Here the authors show that variations in developmental self-reactivity of CD8+ T cells influence their differentiation into Tc17 cells in inflammatory conditions.
- Gil-Woo Lee
- , Young Ju Kim
- & Jae-Ho Cho
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Article
| Open AccessMonoclonal antibodies targeting sites in respiratory syncytial virus attachment G protein provide protection against RSV-A and RSV-B in mice
Effective antibodies targeting various respiratory syncytial virus (RSV) proteins are needed to address public health burden of RSV. Here the authors shows that in addition to the currently approved F-targeting monoclonal antibodies, anti-G cross-reactive monoclonal antibodies to RSV-A and RSV-B strains can provide cross-protection and prevent from RSV disease.
- Youri Lee
- , Laura Klenow
- & Surender Khurana
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