Applied immunology

  • Article
    | Open Access

    Successful cancer immune therapy correlates with a T cell-inflamed tumour microenvironment. Authors show here that co-administration of a self-adjuvanting protein vaccine and an antigen-expressing oncolytic virus in an optimised regimen strongly enhances T cell immunogenicity and may turn non-inflamed tumours proinflammatory and less resistant to checkpoint blockade therapy.

    • Krishna Das
    • , Elodie Belnoue
    •  & Guido Wollmann
  • Article
    | Open Access

    T regulatory (Treg) cells can differentiate into effector Treg (eTreg) cells that might be functional in inflammatory diseases. Using RNA sequencing and epigenetic profiling, the authors show that eTreg signatures in juvenile idiopathic arthritis joints are similar to tumour microenvironment (TME) Treg cells and are affected by tissue-specific epigenetic regulation.

    • Gerdien Mijnheer
    • , Lisanne Lutter
    •  & Femke van Wijk
  • Article
    | Open Access

    Red blood cells (RBCs) have unique properties that have been exploited for therapeutic uses. Here the authors engineer RBCs to co-express tumor associated antigens on MHC I, 4-1BBL and IL-12, generating artificial antigen presenting cells that can induce antigen-specific T cell responses and antitumor immune responses in preclinical models.

    • Xuqing Zhang
    • , Mengyao Luo
    •  & Tiffany F. Chen
  • Article
    | Open Access

    Population-based studies of SARS-CoV-2 seroprevalence are needed to understand levels of immunity and antibody dynamics. Here, the authors show that the seroprevalence in Bonn, Germany was low (<1%) following the first epidemic wave, and that neutralising antibodies waned within a few months.

    • N. Ahmad Aziz
    • , Victor M. Corman
    •  & Monique M. B. Breteler
  • Article
    | Open Access

    Pathogenesis of steroid-resistant gut acute graft-versus-host-disease (SR-Gut-aGVHD) remains unclear., Here the authors show in mouse models that dysbiosis caused by the expansion of Th/Tc22, as well as depletion of CX3CR1hi mononuclear phagocytes resulted from the reduction of Th/Tc1, contributes to SR-Gut-aGVHD onset.

    • Qingxiao Song
    • , Xiaoning Wang
    •  & Defu Zeng
  • Article
    | Open Access

    Monitoring changes in immune phenotype during the progression of multiple sclerosis can provide insight into disease progression and inform treatment. Here the authors develop engineered biomaterial-based immunological niches for easy access to innate immune cells in a mouse model of multiple sclerosis.

    • Aaron H. Morris
    • , Kevin R. Hughes
    •  & Lonnie D. Shea
  • Article
    | Open Access

    Single-cell technologies are increasingly prominent in clinical applications, but predictive modelling with such data in large cohorts has remained computationally challenging. We developed a new algorithm, ‘VoPo’, for predictive modelling and visualization of single cell data for translational applications.

    • Natalie Stanley
    • , Ina A. Stelzer
    •  & Nima Aghaeepour
  • Article
    | Open Access

    Anti-Ly6G or ant-Gr1 antibodies are commonly used to deplete neutrophils in vivo. Here the authors provide mechanistic insight into why these approaches may not specifically or durably reduce the number of neutrophils in mice, and also present a new method that overcomes these limitations to have potentially wide applicability in experimental studies.

    • Gael Boivin
    • , Julien Faget
    •  & Etienne Meylan
  • Article
    | Open Access

    Chronic graft versus host disease (cGvHD) is a major cause of morbidity and mortality in allogeneic bone marrow transplantation. Here the authors identify a recurrent activating mTOR mutation in expanded donor T-cell clones of 3 cGvHD patients, which suggests somatic mutations may contribute to GvHD pathogenesis and opens avenues to targeted therapies.

    • Daehong Kim
    • , Giljun Park
    •  & Satu Mustjoki
  • Article
    | Open Access

    Antibodies expressed in the cytosol often form insoluble aggregates, which makes it hard to target intracellular proteins. Here the authors engineer an ultra-stable cytoplasmic antibody (STAND) with a low isoelectric point that can be used in vivo.

    • Hiroyuki Kabayama
    • , Makoto Takeuchi
    •  & Katsuhiko Mikoshiba
  • Article
    | Open Access

    Recombinant MHC class II molecules are instrumental in antigen-specific T-cell identification assays and showed efficacy as experimental medicines. Here, the authors engineer MHC class II molecules with species-specific knob-into-hole heteromerization domains, enabling a translatable purification process with improved stability, yields, and biological potency.

    • Pau Serra
    • , Nahir Garabatos
    •  & Pere Santamaria
  • Article
    | Open Access

    The authors show an important role for iron in B cell proliferation via histone 3 lysine 9 (H3K9) demethylation at the cyclin E1 promoter. Using a measles vaccination murine model, they show that iron-deficient individuals have a significantly reduced antibody response to the vaccine when compared to iron-normal controls.

    • Yuhang Jiang
    • , Cuifeng Li
    •  & Xiaoren Zhang
  • Article
    | Open Access

    Neutrophils and macrophages are both involved in the initiation of inflammation, but whether and how they may participate in inflammation resolution is unclear. Here the authors show that neutrophils may mediate the conversion of macrophage into a pro-resolution phenotype via reactive oxygen species production to promote liver repair.

    • Wenting Yang
    • , Yuandong Tao
    •  & Li Tang
  • Article
    | Open Access

    Hematopoietic stem cell (HSC) transplantation is a desirable treatment for many non-malignant and malignant diseases, but its use requires preconditioning of recipients with irradiation or chemotherapy that often induces high toxicity. Here the authors show that antibody-drug-conjugate to CD117, a HSC marker, allows specific and efficient preconditioning for HSC therapy.

    • Agnieszka Czechowicz
    • , Rahul Palchaudhuri
    •  & Derrick J. Rossi
  • Article
    | Open Access

    Giardia lamblia express a dense coat of variant-specific surface proteins (VSPs) on trophozoites that protects the parasite inside the host´s intestine. Here the authors show that stability and immunomodulatory properties of VSPs can be exploited to both protect and adjuvant vaccine antigens for oral administration.

    • Marianela C. Serradell
    • , Lucía L. Rupil
    •  & Hugo D. Luján
  • Article
    | Open Access

    Antigen present and presented in the structures of the skin can result in immune responses that elicit tolerance, protective immunity or allergy, depending on the immunological context. Here the authors describe a key role for the hair follicle and CD11b+ dendritic cells in the priming of local antigenic tolerance.

    • Leticia Tordesillas
    • , Daniel Lozano-Ojalvo
    •  & M. Cecilia Berin
  • Article
    | Open Access

    Autoantibodies are implicated in autoimmunity, but may also be present in healthy individuals. Here the authors find that the autoantibody specificity signatures against various G protein-coupled receptors are associated with multiple parameters, including disease states, to imply a physiological function in maintaining immune homeostasis.

    • Otavio Cabral-Marques
    • , Alexandre Marques
    •  & Gabriela Riemekasten
  • Article
    | Open Access

    Human leukocyte antigens (HLA) are multi-allelic and polymorphic genes that present antigens to immune cells for inducing protective immunity. Here, using systems biology and structural approaches, the authors show that micropolymorphism of three HLA has effects beyond the modulation of antigen diversity.

    • Patricia T. Illing
    • , Phillip Pymm
    •  & Anthony W. Purcell
  • Article
    | Open Access

    Studying the uterine lymphocyte pool is difficult due to its dynamic nature induced by various pregnancy-related factors. Here the authors provide, using transcriptome data from sorted mouse group 1 innate lymphoid cells (ILC), a molecular atlas of these cells, which implicates tissue-resident natural killer cells as a hub for uterine immune crosstalk.

    • Iva Filipovic
    • , Laura Chiossone
    •  & Francesco Colucci
  • Article
    | Open Access

    Immunogenicity of AAV vectors renders repeated AAV dosing ineffective. Here the authors show that coadministration of nanoparticle-encapsulated rapamycin overcomes AAV immunogenicity through Treg induction, enabling efficient AAV redosing in mice and nonhuman primates.

    • Amine Meliani
    • , Florence Boisgerault
    •  & Federico Mingozzi
  • Article
    | Open Access

    Current anti-venoms against black mamba (Dendroaspis polylepis) bites are animal-derived and associated with several limitations. Here, Laustsen and colleagues develop an experimental recombinant anti-venom based on oligoclonal human IgG antibodies and establish its potential protective value in neutralizing dendrotoxin-mediated neurotoxicity using venom challenge in vivo models.

    • Andreas H. Laustsen
    • , Aneesh Karatt-Vellatt
    •  & John McCafferty
  • Article
    | Open Access

    Eosinophils are important mediators of allergic responses, but how they are recruited to the inflamed site is still unclear. Here the authors show that CD103+ cDC1 cells secrete CCL17 and CCL22 for eosinophil recruitment, with this process promoted by CD24CD11b+ DC2s in the early phase but suppressed by CD24+ cDC2s in the late phase.

    • Shuying Yi
    • , Jing Zhai
    •  & Hua Tang
  • Article
    | Open Access

    Vitamin E metabolites are proposed to have signalling capacity, but how they may regulate immune responses is still unclear. Here the authors show that a vitamin E metabolite, α-T-13′-COOH, can inhibit 5-lipoxygenase and thereby suppress the synthesis of lipid mediators of immune activation and inflammatory responses.

    • Helmut Pein
    • , Alexia Ville
    •  & Andreas Koeberle
  • Article
    | Open Access

    Pulmonary alveolar proteinosis (PAP) is associated with defective macrophage clearance of surfactant. Here, the authors show that patients with PAP have altered cholesterol-to-phospholipid ratio in their surfactant, and that more importantly, statin therapy and reduction of cholesterol accumulation in macrophages can ameliorate PAP in both humans and mice.

    • Cormac McCarthy
    • , Elinor Lee
    •  & Bruce C. Trapnell
  • Article
    | Open Access

    Lymphotoxin beta receptor (LTβR) signalling regulates leukocyte migration through the lymphatic endothelial layers. Here, the authors show that treatment of an LTβR-derived decoy peptide can target the non-classical NFκB pathway to inhibit T cell and dendritic cell migration and ameliorate contact hypersensitivity in mouse models.

    • Wenji Piao
    • , Yanbao Xiong
    •  & Jonathan S. Bromberg
  • Article
    | Open Access

    Testosterone deficiency is associated with autoimmunity and increased B cell numbers, but the underlying mechanism is unclear. Here the authors show that testosterone may modulate the production of B cell survival factor BAFF by fibroblastic reticular cells via regulation of splenic neurotransmitter levels.

    • Anna S. Wilhelmson
    • , Marta Lantero Rodriguez
    •  & Åsa Tivesten
  • Article
    | Open Access

    BAFF is an important cytokine for B cell survival, and is a therapeutic target for autoimmune disorders. Here the authors show that a 'flap' region of BAFF converts BAFFR binding events into survival signals and, with structural data, that this ‘flap’ differentially modulates binding of drugs such as belimumab or atacicept.

    • Michele Vigolo
    • , Melissa G. Chambers
    •  & Pascal Schneider
  • Article
    | Open Access

    CD28 transmits co-stimulatory signals for the activation of both mouse and human T cells, but in vivo hyperactivation of CD28 has opposite effects on system immunity. Here, the authors show that a single amino acid difference between mouse and human CD28 dictates this function distinction via differential recruitment of Nck.

    • Nicla Porciello
    • , Paola Grazioli
    •  & Loretta Tuosto
  • Article
    | Open Access

    Obesity can affect bone marrow cell differentiation and the generation of myeloid and lymphoid cells. Here, the authors show that diet and obesity, as well as low-dose lipopolysaccharide, can alter Toll-like receptor 4 signaling bone marrow cells to skew the myeloid-lymphoid homeostasis in mice.

    • Ailing Liu
    • , Minhui Chen
    •  & Lisa Borghesi
  • Article
    | Open Access

    B cells are important for antigen presentation and antibody production in humoral immunity, but are also increasingly recognized for their immune regulatory functions. Here the authors show that HIF-1α, a hypoxia-induced transcription factor, is important for controlling IL-10 induction in and immune-suppressive activity of B cells.

    • Xianyi Meng
    • , Bettina Grötsch
    •  & Aline Bozec
  • Article
    | Open Access

    Immune checkpoint blockade (ICB) therapies can unleash anti-tumour T-cell responses. Here the authors show, by integrating MHC tetramer multiplexing, mass cytometry and high-dimensional analyses, that neoantigen-specific, tumour-infiltrating T cells are highly heterogeneous and are subjected to ICB modulations.

    • M. Fehlings
    • , Y. Simoni
    •  & E. W. Newell
  • Article
    | Open Access

    Tumour-specific T cells can be expandedin vitroand adoptively transferred for therapy, but this strategy is limited by induction of short-lived T cell populations. Here the authors activate Notch signalling in cultured mouse or human T cells, resulting in the production of a long-lived stem cell memory T cell population that can fight tumours in mice.

    • Taisuke Kondo
    • , Rimpei Morita
    •  & Akihiko Yoshimura
  • Article
    | Open Access

    Host tropism and cell entry of pathogenic coronaviruses are mediated by their envelope spike (S) proteins. Here the authors present structural analyses of trimeric MERS-CoV and SARS-CoV S proteins in pre-fusion conformation, and reveal two states of the receptor binding domain that suggest new avenues for the generation of neutralizing antibodies.

    • Yuan Yuan
    • , Duanfang Cao
    •  & George F. Gao
  • Article
    | Open Access

    In vivo imaging of inflammation is crucial for detection and monitoring of many pathologies and noninvasive macrophage quantification has been suggested as a possible approach. Here Keliher et al. describe novel polyglucose nanoparticle tracers that are rapidly excreted by the kidney and with high affinity for macrophages in atherosclerotic plaques.

    • Edmund J. Keliher
    • , Yu-Xiang Ye
    •  & Matthias Nahrendorf
  • Article
    | Open Access

    Hybridomas are widely used for antibody screening and production due to their genetic stability and rapid proliferation. Here the authors demonstrate the rapid reprogramming of antibody specificity in hybridomas using CRISPR-Cas9.

    • Mark Pogson
    • , Cristina Parola
    •  & Sai T. Reddy
  • Article
    | Open Access

    The development of native-like envelope trimers has been a major focus in the efforts to produce HIV vaccines. Here the authors demonstrate the production and characterization of virus-like nanoparticles displaying trimeric HIV-1 antigens with the potential to elicit broadly neutralizing antibodies.

    • Linling He
    • , Natalia de Val
    •  & Jiang Zhu
  • Article
    | Open Access

    Immunologically-active glycans are promising vaccine candidates but can be difficult to synthesize. Here, the authors show that pentavalent display of a minimal disaccharde epitope on a chemical scaffold can mimic a native C. difficileglycan antigen, representing a simple approach to synthetic vaccine production.

    • Felix Broecker
    • , Jonas Hanske
    •  & Peter H. Seeberger
  • Article
    | Open Access

    BCG vaccine confers only partial protection against tuberculosis. Here the authors show that the risk of tuberculosis infection and progression to disease in BCG-immunized children positively correlates with the frequency of activated HLA-DR+CD4+T cells.

    • Helen A. Fletcher
    • , Margaret A. Snowden
    •  & Helen McShane
  • Article
    | Open Access

    Type 1 diabetes is associated with the loss of self-tolerance to the insulin-producing β-cells in the pancreas. Here the authors show that vaccination with insulin mimetopes can induce human insulin-specific regulatory T cells to mediate tolerance in a humanized mouse model.

    • Isabelle Serr
    • , Rainer W. Fürst
    •  & Carolin Daniel
  • Article
    | Open Access

    Ageing is associated with poor responses to vaccines but the underlying mechanism remains unclear. Here the authors use a systems-based approach to define molecular signatures present before vaccination that correlate with non-responsiveness to hepatitis B vaccination in healthy, elderly adults.

    • Slim Fourati
    • , Razvan Cristescu
    •  & Rafick-Pierre Sékaly
  • Article
    | Open Access

    Respiratory syncytial virus (RSV) is a highly contagious childhood pathogen of the respiratory tract for which no vaccine is currently available. Here the authors present a strategy to stabilize the RSV F protein in a prefusion conformation that can elicit a strong protective immune response in animal models.

    • Anders Krarup
    • , Daphné Truan
    •  & Johannes P. M. Langedijk
  • Article
    | Open Access

    The availability of high-yield virus strains remains an important bottleneck in the rapid production of influenza vaccines. Here, the authors report the development of influenza A vaccine backbone that improves the virus yield of various seasonal and pandemic influenza vaccine strains in cell culture.

    • Jihui Ping
    • , Tiago J.S. Lopes
    •  & Yoshihiro Kawaoka