Immune cell death

  • Article
    | Open Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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 Access

    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