Featured
-
-
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
-
Article
| Open AccessMyeloid-derived suppressor cell mitochondrial fitness governs chemotherapeutic efficacy in hematologic malignancies
Myeloid derived suppressor cells (MDSC) are associated with tumourigenesis and therapy response. Here, the authors show that beta 2-adrenergic receptor activation in MDSC leads to metabolic rewiring which regulates chemotherapy response in preclinical models of blood cancer.
- Saeed Daneshmandi
- , Jee Eun Choi
- & Hemn Mohammadpour
-
Article
| Open AccessApoptosis-mediated ADAM10 activation removes a mucin barrier promoting T cell efferocytosis
Mucins on the surface of healthy T cells limit their phagocytic uptake by macrophages. Here the authors show that upon apoptosis induction in T cells, surface mucins are cleaved and released by ADAM10 to promote efferocytosis of the apoptotic cells.
- Linnea Z. Drexhage
- , Shengpan Zhang
- & Quentin J. Sattentau
-
Article
| Open AccessGasdermin E dictates inflammatory responses by controlling the mode of neutrophil death
Apoptotic and lytic cell death pathways are both utilised in the removal of damaged cells; however, the downstream inflammatory outcomes widely vary according to the chosen pathway. Here authors show that in mice with genetic deletion of Gasdermin E specifically in neutrophils, these cells undergo apoptosis rather than pyroptotic cell death upon senescence, with consequential attenuation of reactive inflammatory responses.
- Fengxia Ma
- , Laxman Ghimire
- & Hongbo R. Luo
-
Article
| Open AccessIKKε and TBK1 prevent RIPK1 dependent and independent inflammation
TBK1 and IKKε are involved in the regulation of a range of cellular and inflammatory processes. Here Eren and colleagues discern a role for IKKε in preventing RIPK1-dependent and RIPK1-independent inflammation in mice lacking TBK1 kinase activity.
- Remzi Onur Eren
- , Göksu Gökberk Kaya
- & Manolis Pasparakis
-
Article
| Open AccessCisplatin toxicity is counteracted by the activation of the p38/ATF-7 signaling pathway in post-mitotic C. elegans
In contrast to mammalian cells, C. elegans models can be useful because of cells being post-mitotic in adults. Here the authors show activation of the p38 pathway in cisplatin resistant adult animals and characterise the proteins upstream and downstream of the p38 MAPK signalling pathway that are involved in the cisplatin response.
- Dorota Raj
- , Bashar Kraish
- & Peter Naredi
-
Article
| Open AccessLoss of Zfp335 triggers cGAS/STING-dependent apoptosis of post-β selection thymocytes
T cell development involves extensive proliferation of developing thymocytes. Here, the authors demonstrate that the transcription factor Zfp335 regulates the survival post-β-selection thymocytes via the cGAS/STING pathway.
- Jeremy J. Ratiu
- , William E. Barclay
- & Yuan Zhuang
-
Article
| Open AccessCovalent TCR-peptide-MHC interactions induce T cell activation and redirect T cell fate in the thymus
Differentiation and activation of T cells are normally modulated by non-covalent interactions between T cell receptor (TCR) and antigenic peptides. Here the authors use step-wise mutations, biochemical characterization and structural insights to describe the contributions of natural covalent bonds between TCR and antigenic peptides during these processes.
- Christopher Szeto
- , Pirooz Zareie
- & Stephen R. Daley
-
Article
| Open AccessIntegrative multi-omics and drug response profiling of childhood acute lymphoblastic leukemia cell lines
Childhood acute lymphoblastic leukemia is characterised by a range of genetic aberrations. Here, the authors use multi-omics profiling of ALL cell lines to connect molecular phenotypes and drug responses to provide an interactive resource of drug sensitivity.
- Isabelle Rose Leo
- , Luay Aswad
- & Rozbeh Jafari
-
Article
| Open AccessThe arginine methyltransferase PRMT7 promotes extravasation of monocytes resulting in tissue injury in COPD
Chronic obstructive pulmonary disease is a progressive and incurable chronic condition that involves accumulation of inflammatory macrophages in the lung tissue. Authors here show in mouse models of lung disease that PRMT7, a protein arginine methyltransferase, is an important regulator of recruitment and the pro-inflammatory phenotype of macrophages.
- Gizem Günes Günsel
- , Thomas M. Conlon
- & Ali Önder Yildirim
-
Article
| Open AccessInflammasome-mediated GSDMD activation facilitates escape of Candida albicans from macrophages
Inflammasome signalling has been shown to protect Candida albicans during infection and as such limits inflammasome inhibitors in this context. Here the authors implicate Gasdermin D in C.ablicans immune evasion and suggests its targeting therapeutically.
- Xionghui Ding
- , Hiroto Kambara
- & Hongbo R. Luo
-
Article
| Open AccessWdr1 and cofilin are necessary mediators of immune-cell-specific apoptosis triggered by Tecfidera
The mechanism-of-action of many electrohilic drugs remains poorly understood. Here, the authors use a redox-targeting approach to elucidate the basis for the innate immune cell toxicity of dimethyl fumarate, showing that it modifies Keap1 to trigger mitochondrial-targeted neutrophil/macrophage apoptosis.
- Jesse R. Poganik
- , Kuan-Ting Huang
- & Yimon Aye
-
Article
| Open AccessZBP1 promotes LPS-induced cell death and IL-1β release via RHIM-mediated interactions with RIPK1
Yersiania YopJ protein has been shown to drive caspase-8-mediated pyroptosis. Here the authors show a precise mechanism of this non-canonical cell death pathway that is controlled by a TRIF-dependent complex of FADD, RIPK1, caspase-8 and ZBP1.
- Hayley I. Muendlein
- , Wilson M. Connolly
- & Alexander Poltorak
-
Article
| Open AccessClearance of HIV infection by selective elimination of host cells capable of producing HIV
The latent human immunodeficiency virus (HIV) reservoir in patients poses a problem for HIV cure. Here, Li et al. show that a combination of compounds inducing viral reactivation and cell death, inhibiting autophagy and blocking new infections can eliminate HIV infection in 50% of humanized HIV infected mice and in blood samples from infected patients.
- Min Li
- , Wei Liu
- & Jin Wang
-
Article
| Open AccessPlasma membrane damage causes NLRP3 activation and pyroptosis during Mycobacterium tuberculosis infection
Inflammasome activation is a response to bacterial infection but can cause damage and spread infection. Here, the authors use live single-cell imaging to show two mechanisms by which M. tuberculosis causes damage to human macrophage cell plasma membranes, resulting in activation of the NLRP3 inflammasome, pyroptosis and release of infectious particles.
- Kai S. Beckwith
- , Marianne S. Beckwith
- & Trude H. Flo
-
Article
| Open AccessN-GSDMD trafficking to neutrophil organelles facilitates IL-1β release independently of plasma membrane pores and pyroptosis
In macrophages, IL-1β secretion is mediated by N-GSDMD pores in the plasma membrane (PM). Here the authors show that in neutrophils, IL-1β secretion occurs in the absence of PM pores, via autophagosomes; N-GSDMD does not traffic to PM but to azurophilic granules, thereby releasing neutrophil elastase which cleaves further N-GSDMD into alternative fragments.
- Mausita Karmakar
- , Martin Minns
- & Eric Pearlman
-
Article
| Open AccessCaspase-11 promotes allergic airway inflammation
Caspase 11 activation involves transcriptional upregulation and proteolytic cleavage. Here the authors show that prostaglandin E2 prevents caspase-11-mediated pyroptosis, blocking caspase-11 mRNA and protein upregulation in macrophages and in vivo, and that mice lacking caspase-11 are strongly protected from allergic airway inflammation.
- Zbigniew Zasłona
- , Ewelina Flis
- & Luke A. J. O’Neill
-
Article
| Open AccessIdentification of a genomic enhancer that enforces proper apoptosis induction in thymic negative selection
Autoreactive T cells are deleted in the thymus via thymic negative selection and Bim-mediated apoptosis. Here the authors identify a cis-acting enhancer, EBAB, that is essential for proper Bim expression and apoptosis induction, and show that EBAB deficiency specifically impairs thymic negative selection without affecting peripheral T cell homeostasis.
- Miki Arai Hojo
- , Kyoko Masuda
- & Shinpei Kawaoka
-
Article
| Open AccessMacrophage achieves self-protection against oxidative stress-induced ageing through the Mst-Nrf2 axis
Immune cells produce reactive oxygen species (ROS) to eliminate pathogens, but cell-spontaneous death and ageing may also be induced. Here the authors show that, upon sensing ROS, Mst1/2 kinases modulate the activity of Nrf2 transcription factor and downstream genetic programs to protect mouse macrophages from death and ageing.
- Ping Wang
- , Jing Geng
- & Lanfen Chen
-
Article
| Open AccessCorticosteroids inhibit Mycobacterium tuberculosis-induced necrotic host cell death by abrogating mitochondrial membrane permeability transition
Corticosteroids are host-directed drugs that enhance survival of tuberculosis patients through unclear mechanisms. Here, Gräb et al. show that corticosteroids inhibit necrotic death of cells infected with Mycobacterium tuberculosis by facilitating MKP-1-dependent dephosphorylation of p38 MAPK.
- Jessica Gräb
- , Isabelle Suárez
- & Jan Rybniker
-
Article
| Open AccessPRMT5 is essential for B cell development and germinal center dynamics
Protective antibody responses depend critically on proper B cell development and differentiation at multiple stages. Here the authors show that a protein arginine methyltransferase, Prmt5 uses multiples pathways to prevent death of immature B cells, yet modulates, in p53-independent manners, the survival and differentiation of mature B cells.
- Ludivine C. Litzler
- , Astrid Zahn
- & Javier M. Di Noia
-
Article
| Open AccessSTING-dependent sensing of self-DNA drives silica-induced lung inflammation
Silica particles induce intereukin-1 (IL-1) response to contribute to lung inflammation, but the underlying mechanism is unclear. Here the authors show that silica induces cell death and release of mitochondria and genomic DNA, which are sensed by STING with or without involving cGAS, respectively, for IL-1 induction and lung inflammation.
- Sulayman Benmerzoug
- , Stéphanie Rose
- & Valerie F. J. Quesniaux
-
Article
| Open AccessStudies into the mechanism of measles-associated immune suppression during a measles outbreak in the Netherlands
The mechanisms by which measles virus infection induces transient immune suppression in humans are poorly understood. Here, Laksono and colleagues characterise the pathogenesis of measles-associated immune suppression in unvaccinated children, and shed new light on the long-term effects of measles on the host.
- Brigitta M. Laksono
- , Rory D. de Vries
- & Rik L. de Swart
-
Article
| Open AccessTreatment with mRNA coding for the necroptosis mediator MLKL induces antitumor immunity directed against neo-epitopes
Necroptosis has immunogenic cell death properties. Here, the authors show that the intra-tumor delivery of mRNA that codes for the necroptosis effector MLKL triggers neo-epitope-specific anti-tumor T cell responses and inhibits primary tumor growth and lung metastasis.
- Lien Van Hoecke
- , Sandra Van Lint
- & Xavier Saelens
-
Article
| Open AccessThe E3 ubiquitin ligase Pellino2 mediates priming of the NLRP3 inflammasome
The NLRP3 inflammasome is important for inducing IL-1β and IL-18 inflammatory responses. Here the authors show, by generating and characterizing Peli2 deficient mice and immune cells, that an E3 ubiquitin ligase Pellino2 promotes inflammasome priming by inducing NLRP3 ubiquitination and by targeting IRAK1.
- Fiachra Humphries
- , Ronan Bergin
- & Paul N. Moynagh
-
Article
| Open AccessPandemic H1N1 influenza A viruses suppress immunogenic RIPK3-driven dendritic cell death
The differences in virus-host interactions resulting in distinct pathogenicity of seasonal and pandemic influenza A viruses (IAV) are not well understood. Here, the authors show that the hemagglutinin segment from pandemic, but not seasonal, IAV suppresses RIPK3-mediated dendritic cell death, thereby reducing T cell activation.
- Boris M. Hartmann
- , Randy A. Albrecht
- & Stuart C. Sealfon
-
Article
| Open AccessDNA-binding of the Tet-transactivator curtails antigen-induced lymphocyte activation in mice
Tet-transactivators are used for direct regulation of gene expression, RNA interference and for CRISPR/Cas9-based systems. Here the authors show that DNA-bound Tet-transactivators can induce cell death in antigen-activated lymphocytes in vivo, putting into question the use of, and in vivo data generated with, these molecular tools.
- Eleonora Ottina
- , Victor Peperzak
- & Andreas Villunger
-
Article
| Open AccessNCoR1 restrains thymic negative selection by repressing Bim expression to spare thymocytes undergoing positive selection
Thymocytes are screened by two processes, termed positive and negative selections, which are permissive only for immature thymocytes with intermediate avidity to the selecting ligands. Here the authors show that the nuclear receptor NCoR1 suppresses Bim1 to inhibit negative selection and promote thymocyte survival.
- Jianrong Wang
- , Nanhai He
- & Qibin Leng
-
Article
| Open AccessSignalling strength determines proapoptotic functions of STING
The cGAS/STING signalling pathway is responsible for sensing intracellular DNA and activating downstream inflammatory genes. Here the authors show mouse primary T cells and T leukaemia are hyperresponsive to STING agonist, and this strong STING signalling is associated with apoptosis induction.
- Muhammet F. Gulen
- , Ute Koch
- & Andrea Ablasser
-
Article
| Open AccessFas/CD95 prevents autoimmunity independently of lipid raft localization and efficient apoptosis induction
Fas drives apoptosis and mutations in this receptor can cause autoimmunity through failure of cell death. Here, the authors uselpr/lprmice with palmitoylation-defective mutant Fas to provide evidence that Fas might limit spontaneous autoimmunity through a non-apoptotic mechanism.
- Anthony C. Cruz
- , Madhu Ramaswamy
- & Richard M. Siegel