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| Open AccessInvariant γδTCR natural killer-like effector T cells in the naked mole-rat
Naked mole-rats are long-lived rodents known to be resistant to the development of cancer, yet their immune system remains poorly explored. Here, the authors identify natural killer-like effector γδ T cells that express a dominant γδ T cell receptor and may serve a role in tumour immunosurveillance.
- Guillem Sanchez Sanchez
- , Stephan Emmrich
- & David Vermijlen
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Article
| Open AccessTlr9 deficiency in B cells leads to obesity by promoting inflammation and gut dysbiosis
Although the function of Toll-like receptor 9 (TLR9) in immunity and inflammation is well-established, its role in obesity is less well-studied. In this study, the authors demonstrate that TLR9 deficiency in B cells is associated with obesity in mice and results in altered frequencies of T and B lymphocyte subsets and gut microbiome dysbiosis.
- Pai Wang
- , Xin Yang
- & Li Wen
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Article
| Open AccessEnhanced CD95 and interleukin 18 signalling accompany T cell receptor Vβ21.3+ activation in multi-inflammatory syndrome in children
Multi-Inflammatory Syndrome in Children (MIS-C) is a severe post-infectious presentation related to SARS-CoV-2 infection. Here authors used multi-omics approaches to characterise MIS-C cases and found increased CD95 and IL-18 signalling accompanying the expansion of TCR Vβ 21.3+ T cells.
- Zhenguang Zhang
- , Iain R. L. Kean
- & Nazima Pathan
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Article
| Open AccessOriginal COVID-19 priming regimen impacts the immunogenicity of bivalent BA.1 and BA.5 boosters
Waning immunity and the emergence of the SARS-CoV-2 Omicron lineage led to reduced vaccine effectiveness and required vaccine updates. Here, the authors assess how different priming regimens affect the immunogenicity of BA.1 and BA.5 bivalent boosters.
- Luca M. Zaeck
- , Ngoc H. Tan
- & Rory D. de Vries
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Article
| Open AccessRecruitment of plasma cells from IL-21-dependent and IL-21-independent immune reactions to the bone marrow
The mechanisms driving B cell differentiation into resident bone marrow plasma cells (BMPC) remain unclear. Here the authors use single cell sequencing and BMPC phenotyping to infer developmental pathways and regulation by IL-21 in germinal centres to promote maintenance of BMPC after vaccination in humans.
- Marta Ferreira-Gomes
- , Yidan Chen
- & Mir-Farzin Mashreghi
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Article
| Open AccessLong-term relapse-free survival enabled by integrating targeted antibacteria in antitumor treatment
Tumor-resident intracellular microbiota (TRIM) could be a potential target for anticancer treatment. Here the authors report Au@Ag2Se nano-assemblies enabling bacterial killing, tumor inhibition and immune regulation in tumor microenvironment.
- Yuanlin Wang
- , Yaqian Han
- & Miao Yu
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Article
| Open AccessSustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity
The role of IFN signaling in SARS-CoV-2 infection and outcome is still debated. Here, the authors longitudinally profiled plasma samples from hospitalized patients and show that a persistent inflammatory response is linked to delayed generation of adaptive immunity and increased risk of death when coupled with severe infection.
- Elsa Brunet-Ratnasingham
- , Sacha Morin
- & Daniel E. Kaufmann
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Article
| Open AccessADAM9 promotes type I interferon-mediated innate immunity during encephalomyocarditis virus infection
Mice lacking A Disintegrin and Metalloproteinase 9 (ADAM9) do not mount Type 1 interferon responses against encephalomyocarditis infection. Here, Bazzone et al show that ADAM9 regulates innate immune responses via by MDA5.
- Lindsey E. Bazzone
- , Junji Zhu
- & Evelyn A. Kurt-Jones
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Article
| Open AccessCD5L as a promising biological therapeutic for treating sepsis
Authors explore the utility of CD5L for treating experimental sepsis. CD5L deficiency exacerbates experimental sepsis. Conversely, administration of recombinant CD5L in WT mice augments neutrophil function, enhances bacterial control, and mitigates inflammation, leading to substantial improvements in disease outcomes.
- Liliana Oliveira
- , M. Carolina Silva
- & Alexandre M. Carmo
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Article
| Open AccessOctyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways
The use of oncolytic viruses as a therapy for cancer is limited by mechanisms inhibiting viral replication in the tumor. Here, the authors show that a chemical derivative of itaconate, 4-octyl itaconate, increases oncolytic virus VSVΔ51 efficacy in various cancer models, through decreasing antiviral immunity.
- Naziia Kurmasheva
- , Aida Said
- & David Olagnier
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Article
| Open AccessDouble-negative B cells and DNASE1L3 colocalise with microbiota in gut-associated lymphoid tissue
Intestinal homeostasis is maintained by interactions between the gut-associated lymphoid tissue and the resident flora. Here Montorsi et al use multiplexed single cell omics to describe double negative type 2 B cells and DNASE1L3-expressing dendritic cells that interact and associate with microbiota on the human gut antigenic front line.
- Lucia Montorsi
- , Michael J. Pitcher
- & Jo Spencer
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Article
| Open AccessPremature skewing of T cell receptor clonality and delayed memory expansion in HIV-exposed infants
Here, Dzanibe et al show that in utero HIV/ARV exposure sequentially disrupts infant immunologic trajectories, beginning with NK cells that predict vaccine antibody responses and followed by delayed T cell memory maturation linked to skewed TCR clonality.
- Sonwabile Dzanibe
- , Aaron J. Wilk
- & Clive M. Gray
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Article
| Open AccessSafety, immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled trials
In this randomized, controlled integrated phase 1/2/3a/3b clinical trial, the authors show that the self-amplifying mRNA COVID-19 vaccine ARCT-154 shows good immunogenicity and is safe and efficient against COVID-19 (57% against any COVID-19, and 95% against severe COVID-19).
- Nhân Thị Hồ
- , Steven G. Hughes
- & Xuan-Hung Nguyen
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Article
| Open AccessThe structural basis for 2′−5′/3′−5′-cGAMP synthesis by cGAS
Here, the authors provide structural and biochemical data describing the mechanism through which cGAS synthesizes 2′−5′/3′−5′-cGAMP.
- Shuai Wu
- , Sandra B. Gabelli
- & Jungsan Sohn
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Article
| Open AccessPretreatment with IL-15 and IL-18 rescues natural killer cells from granzyme B-mediated apoptosis after cryopreservation
Natural killer (NK) cells are assessed for various therapies, but sub-optimal cryopreservation dampens their clinical feasibility. Here the authors show that pretreating human NK cells with IL-15/IL-18 prior to cryopreservation improves NK cell post-thaw viability and functions, potentially via anti-apoptosis gene induction and granzyme B degranulation.
- Abdulla Berjis
- , Deeksha Muthumani
- & Neil C. Sheppard
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Article
| Open AccessAn integrated technology for quantitative wide mutational scanning of human antibody Fab libraries
Limited experimental platforms exist for assessing quantitative sequence-function relationships for multiple antibodies. Here, authors develop a deep-sequencing based technology called MAGMA-seq, that determines the quantitative properties of antibody libraries.
- Brian M. Petersen
- , Monica B. Kirby
- & Timothy A. Whitehead
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Article
| Open AccessThe STING agonist IMSA101 enhances chimeric antigen receptor T cell function by inducing IL-18 secretion
It has been previously suggested that STING agonists can improve response to CAR-T therapy. Here the authors report the characterization of the STING agonist IMSA101, showing that STING-induced IL18 secretion enhances CAR-T activity in preclinical cancer models.
- Ugur Uslu
- , Lijun Sun
- & Carl H. June
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Article
| Open AccessTFPI from erythroblasts drives heme production in central macrophages promoting erythropoiesis in polycythemia
The role of coagulation system in erythropoiesis is not clear. Here, the authors report that an anticoagulant protein TFPI from erythroblasts directs central macrophages to synthesize heme, which in turn promotes erythropoiesis in bone marrow.
- Jun-Kai Ma
- , Li-Da Su
- & Xin-Jiang Lu
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Article
| Open AccessFragment ion intensity prediction improves the identification rate of non-tryptic peptides in timsTOF
Immunopeptidomics is crucial for the discovery of potential immunotherapy and vaccine candidates. Here, the authors generate a ground truth timsTOF dataset to fine-tune the deep learning model Prosit, improving peptide-spectrum match rescoring by up to 3-fold during immunopeptide identification.
- Charlotte Adams
- , Wassim Gabriel
- & Kurt Boonen
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Article
| Open AccessCLK2 mediates IκBα-independent early termination of NF-κB activation by inducing cytoplasmic redistribution and degradation
The NF-kB pathway is strictly regulated to prevent excessive inflammatory and immune responses. Here, Li et al. describe an alternative pathway of negative regulation of p65- driven gene expression.
- Shang-Ze Li
- , Qi-Peng Shu
- & Xiao-Dong Zhang
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Article
| Open AccessHyphal Als proteins act as CR3 ligands to promote immune responses against Candida albicans
Integrin CR3 (CD11b/CD18) is a receptor responsible for recognizing fungal β-glucan. Here, Zhou et al show that the Candida albicans Als family proteins are ligands for the CD11b I domain; an interaction which synergizes with β-glucan to activate CR3.
- Tingting Zhou
- , Norma V. Solis
- & Haoping Liu
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Article
| Open AccessPD-1/CD80+ small extracellular vesicles from immunocytes induce cold tumours featured with enhanced adaptive immunosuppression
Immune checkpoint inhibition is a successful form of immune therapy; however response rates vary widely among individual patients. Here authors show that circulating small extracellular vesicles might contribute to poor response to anti-PD-1 treatment by carrying PD-1 and CD80 which results in higher level of vesicular PD-L1 expression in the circulation at the expense of expression on tumour cell membranes, causing immunosuppression.
- Lin-Zhou Zhang
- , Jie-Gang Yang
- & Gang Chen
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Article
| Open AccessTLR agonists polarize interferon responses in conjunction with dendritic cell vaccination in malignant glioma: a randomized phase II Trial
Autologous tumor lysate (ATL) dendritic cell (DC) vaccination can induce local and systemic anti-tumor immune responses in malignant glioma patients. In this randomized phase II clinical trial, the authors evaluate the effectiveness of adding the TLR agonists, poly-ICLC or resiquimod, to ATL-DC vaccination in patients with newly-diagnosed or recurrent WHO Grade III-IV malignant gliomas.
- Richard G. Everson
- , Willy Hugo
- & Robert M. Prins
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Article
| Open AccessPredicting vaccine effectiveness for mpox
Here, based on a systematic review and meta-analysis, the authors analyze the relationship between vaccine immunogenicity and vaccine protection against mpox and predict the durability of protection after vaccination. This helps inform the optimal vaccine deployment in a health emergency.
- Matthew T. Berry
- , Shanchita R. Khan
- & David S. Khoury
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Article
| Open AccessBacteroidota inhibit microglia clearance of amyloid-beta and promote plaque deposition in Alzheimer’s disease mouse models
The gut microbiota and microglia play critical roles in Alzheimer’s disease (AD). Here, the authors show that Bacteroides fragilis contributes to AD pathogenesis in mouse models by suppressing immune-mediated microglial clearance of amyloid beta.
- Caroline Wasén
- , Leah C. Beauchamp
- & Howard L. Weiner
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Article
| Open AccessA comprehensive genetic map of cytokine responses in Lyme borreliosis
Common genetic variants can affect an individual’s immune response to pathogens. Here, the authors uncover and characterize variants regulating cytokine responses in Lyme Borreliosis in 1,060 patients.
- Javier Botey-Bataller
- , Hedwig D. Vrijmoeth
- & Yang Li
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Article
| Open AccessDistinct cellular immune responses in children en route to type 1 diabetes with different first-appearing autoantibodies
Previous studies have reported heterogeneity in the progression to clinical type 1 diabetes in children who develop either insulin- or glutamic acid decarboxylase-specific antibodies as their first autoantibodies. Here, the authors show that children who later develop disease have distinct characteristics in early immune responses, which are dependent on the type of autoantibodies that appear first.
- Inna Starskaia
- , Milla Valta
- & Riitta Lahesmaa
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Article
| Open AccessReplication competent HIV-guided CRISPR screen identifies antiviral factors including targets of the accessory protein Nef
Innate immune mechanisms are critical for antiviral defense. Here, the authors developed a CRISPR/Cas9-based HIV-driven approach to identify cellular factors compromising viral transcription, assembly, release or infectivity in human T cells. They identify targets of the Nef protein as antiviral factors.
- Caterina Prelli Bozzo
- , Alexandre Laliberté
- & Frank Kirchhoff
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Article
| Open AccessIL-17C is a driver of damaging inflammation during Neisseria gonorrhoeae infection of human Fallopian tube
In pelvic inflammatory disease, host immune responses to Neisseria gonorrhoeae damage Fallopian tube tissue and cause infertility. Here, Garcia et al. show that the cytokine IL-17C induces inflammatory responses, and peptidoglycan fragments reduce transcripts related to tissue integrity.
- Erin M. Garcia
- , Jonathan D. Lenz
- & Joseph P. Dillard
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Article
| 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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