Microbiology, Virology & Host Pathogen Interaction
- Mycobacteria exploit nitric oxide‐induced transformation of macrophages into permissive giant cells
- Kourosh Gharun1,2,
- Julia Senges1,
- Maximilian Seidl1,3,
- Anne Lösslein1,
- Julia Kolter1,2,
- Florens Lohrmann1,4,5,
- Manfred Fliegauf1,
- Magdeldin Elgizouli1,
- Martina Vavra6,
- Kristina Schachtrup1,
- Anna L Illert7,8,
- Martine Gilleron9,
- Carsten J Kirschning10,
- Antigoni Triantafyllopoulou1,5 and
- Philipp Henneke (philipp.henneke{at}uniklinik-freiburg.de)*,1,11
- 1Center for Chronic Immunodeficiency (CCI), Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- 2Faculty of Biology, University of Freiburg, Freiburg, Germany
- 3Department of Pathology, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- 4Spemann Graduate School for Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany
- 5Department of Rheumatology and Clinical Immunology, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- 6Division of Infectious Diseases, Department of Internal Medicine 2, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- 7Department of Medicine I, Medical Center, University of Freiburg, Faculty of Medicine University of Freiburg, Freiburg, Germany
- 8German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany
- 9Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France
- 10Institute of Medical Microbiology, Medical Center, University Duisburg‐Essen, Essen, Germany
- 11Center for Pediatrics and Adolescent Medicine, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- ↵*Corresponding author. Tel: +49 761 270 77640; E‐mail: philipp.henneke{at}uniklinik-freiburg.de
Immunity to mycobacteria triggers granulomas, involving multinucleated giant cells as a unique macrophage species. Dysregulation of the TLR‐induced antimicrobial molecule nitric oxide propagates their transformation by interfering with the DNA damage response.
Synopsis
Immunity to mycobacteria triggers granulomas, involving multinucleated giant cells (MGC) as a unique macrophage species. Dysregulation of the TLR‐induced antimicrobial molecule nitric oxide propagates their transformation by interfering with the DNA damage response.
Nitric oxide (NO) drives the transformation of macrophages into MGC.
The underlying mechanism involves NO‐induced DNA damage and p53 impairment.
MGC show exceptional capacity to ingest apoptotic cells and are permissive for mycobacterial persistence.
EMBO Reports (2017) 18: 2144–2159
- Received February 21, 2017.
- Revision received September 23, 2017.
- Accepted October 2, 2017.
- © 2017 The Authors
- Identification of the centromeres of Leishmania major: revealing the hidden pieces
- Maria‐Rosa Garcia‐Silva1,2,
- Lauriane Sollelis1,2,
- Cameron Ross MacPherson3,4,5,
- Slavica Stanojcic1,2,
- Nada Kuk1,2,
- Lucien Crobu2,
- Frédéric Bringaud6,7,
- Patrick Bastien1,2,8,
- Michel Pagès2,
- Artur Scherf3,4,5 and
- Yvon Sterkers (yvon.sterkers{at}umontpellier.fr)*,1,2,8,9
- 1Department of Parasitology‐Mycology, Faculty of Medicine, University of Montpellier, Montpellier, France
- 2CNRS 5290 ‐ IRD 224 ‐ University of Montpellier (UMR “MiVEGEC”), Montpellier, France
- 3Biology of Host‐Parasite Interactions Unit, Institut Pasteur, Paris, France
- 4CNRS, ERL 9195, Paris, France
- 5INSERM, Unit U1201, Paris, France
- 6Laboratoire de Microbiologie Fondamentale et Pathogénicité (MFP), University of Bordeaux, Bordeaux, France
- 7CNRS, UMR 5234, Bordeaux, France
- 8Department of Parasitology‐Mycology, University Hospital Centre (CHU), Montpellier, France
- 9Present Address: Laboratoire de Parasitologie‐Mycologie, CHU de Montpellier, Montpellier Cedex 5, France
- ↵*Corresponding author. Tel: +33 467 63 55 13; Fax: +33 467 63 00 49; E‐mail: yvon.sterkers{at}umontpellier.fr
LmKKT1 is a Leishmania kinetoplastid kinetochore protein that shows single ChIP‐Seq peaks corresponding to the 36 centromeres. As a centrosomal marker, LmKKT1 is found at the periphery of the nucleolus during interphase and relocates to the spindle poles during mitosis.
Synopsis
LmKKT1 is a Leishmania kinetoplastid kinetochore protein that shows single ChIP‐Seq peaks corresponding to the 36 centromeres. As a centrosomal marker, LmKKT1 is found at the periphery of the nucleolus during interphase and relocates to the spindle poles during mitosis.
LmKKT1 displays “kinetochore‐like” dynamics of intranuclear localization throughout the cell cycle.
LmKKT1 shows single narrow peaks per chromosome that correspond to the centromeres.
Leishmania major centromeres are essentially non‐repetitive and display great inter‐chromosomal sequence heterogeneity.
L. major centromeres are characterised by two conserved motifs and a higher density of retroposons.
EMBO Reports (2017) 18: 1968–1977
- Received March 17, 2017.
- Revision received August 15, 2017.
- Accepted August 28, 2017.
- © 2017 The Authors
- Type VI secretion system MIX‐effectors carry both antibacterial and anti‐eukaryotic activities
- Ann Ray1,2,
- Nika Schwartz3,
- Marcela de Souza Santos1,
- Junmei Zhang1,2,
- Kim Orth1,2,4 and
- Dor Salomon (dorsalomon{at}mail.tau.ac.il)*,3
- 1Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA
- 2Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA
- 3Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- 4Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, USA
- ↵*Corresponding author. Tel: +972 3 6408583; E‐mail: dorsalomon{at}mail.tau.ac.il
Type VI secretion systems are protein delivery apparatuses that mediate predominately bactericidal activities. This study shows that a Vibrio T6SS utilizes a versatile repertoire of effectors to target both competing bacteria and neighbouring eukaryotic cells.
Synopsis
Type VI secretion systems are protein delivery apparatuses that mediate predominately bactericidal activities. This study shows that a Vibrio T6SS utilizes a versatile repertoire of effectors to target both competing bacteria and neighbouring eukaryotic cells.
The Vibrio proteolyticus T6SS1 mediates bacterial killing under warm marine‐like conditions.
The Vibrio T6SS1 delivers a suite of effectors with predicted bactericidal and virulence activities.
A CNF1‐containing Vibrio T6SS1 MIX‐effector induces actin rearrangements and morphological changes upon infection of macrophages.
EMBO Reports (2017) 18: 1978–1990
- Received March 15, 2017.
- Revision received August 14, 2017.
- Accepted August 16, 2017.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Viral taxonomyThe effect of metagenomics on understanding the diversity and evolution of viruses
The effect of metagenomics on understanding the diversity and evolution of viruses
- Philip Hunter, Freelance journalist (ph{at}philiphunter.com)1
The advent of next‐generation sequencing and metagenomics is challenging viral taxonomy to define and characterize viruses along with providing novel insights into the vast diversity of viruses and their evolution.
- © 2017 The Author
- ER remodeling by the large GTPase atlastin promotes vacuolar growth of Legionella pneumophila
- Bernhard Steiner1,
- Anna Leoni Swart1,
- Amanda Welin1,
- Stephen Weber1,
- Nicolas Personnic1,
- Andres Kaech2,
- Christophe Freyre3,
- Urs Ziegler2,
- Robin W Klemm3 and
- Hubert Hilbi (hilbi{at}imm.uzh.ch)*,1
- 1Institute of Medical Microbiology, University of Zürich, Zürich, Switzerland
- 2Center for Microscopy and Image Analysis, University of Zürich, Zürich, Switzerland
- 3Institute of Molecular Life Sciences, University of Zürich, Zürich, Switzerland
- ↵*Corresponding author. Tel: +41 44 634 2650; Fax: +41 44 634 4906; E‐mail: hilbi{at}imm.uzh.ch
The intracellular pathogen Legionella pneumophila replicates within a distinct ER‐associated compartment, the Legionella‐containing vacuole (LCV). The large, dynamin‐like GTPase atlastin3/Sey1 contributes to LCV maturation and growth by promoting ER tubule dynamics and organelle remodeling.
Synopsis
The intracellular pathogen Legionella pneumophila replicates within a distinct ER‐associated compartment, the Legionella‐containing vacuole (LCV). The large, dynamin‐like GTPase atlastin3/Sey1 contributes to LCV maturation and growth by promoting ER tubule dynamics and organelle remodeling.
The ER tubule‐resident large GTPase Atlastin3/Sey1 localizes to LCVs and enhances intracellular replication of L. pneumophila.
Sey1 is dispensable for initial recruitment of ER to PtdIns(4)P‐positive LCVs but promotes subsequent pathogen vacuole expansion.
GTP (but not GDP) triggers the Sey1‐dependent aggregation of purified, ER‐positive LCVs in vitro.
EMBO Reports (2017) 18: 1817–1836
- Received January 5, 2017.
- Revision received July 13, 2017.
- Accepted July 25, 2017.
- © 2017 The Authors
- IFITM3 requires an amphipathic helix for antiviral activity
- Nicholas M Chesarino1,
- Alex A Compton2,3,4,
- Temet M McMichael1,
- Adam D Kenney1,
- Lizhi Zhang1,
- Victoria Soewarna1,
- Matthew Davis1,
- Olivier Schwartz2,3 and
- Jacob S Yount (yount.37{at}osu.edu)*,1
- 1Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA
- 2Virus & Immunity Unit, Department of Virology, Institut Pasteur, Paris, France
- 3CNRS URA 3015, Paris, France
- 4HIV Dynamics and Replication Program, National Cancer Institute, National Institutes of Health, Frederick, MD, USA
- ↵*Corresponding author. Tel: +1 614 688 1639; E‐mail: yount.37{at}osu.edu
Interferon‐induced transmembrane protein 3 (IFITM3) is a cellular factor that blocks virus fusion with cell membranes. This study discovers an amphipathic helix within IFITM3 that is required for its inhibition of infection by diverse pathogenic viruses.
Synopsis
Interferon‐induced transmembrane protein 3 (IFITM3) is a cellular factor that blocks virus fusion with cell membranes. This study discovers an amphipathic helix within IFITM3 that is required for its inhibition of infection by diverse pathogenic viruses.
The amino acids 59–68 of IFITM3 constitute an amphipathic helix.
The amphipathic helix IFITM3 is essential for blocking virus infection, e.g. by influenza A virus, vesicular stomatitis virus and Zika virus.
The IFITM3 amphipathic helix is essential for blocking virus‐mediated membrane fusion.
EMBO Reports (2017) 18: 1740–1751
- Received February 17, 2017.
- Revision received July 18, 2017.
- Accepted July 25, 2017.
- © 2017 The Authors
- Length does matter for cGAS
Recognition of foreign nucleic acids by the immune system is essential to host protection against many viral and bacterial infections. It relies on the capacity of innate immune sensors to selectively distinguish self‐ and non‐self‐nucleic acids, on the basis of a variety of parameters including base modifications, sequence composition, length or subcellular localisation. In this issue of EMBO Reports, Luecke et al [1] describe that the sensing of cytoplasmic double‐stranded DNA by the cyclic GMP–AMP (cGAMP) synthase (cGAS) is much more sensitive for longer fragments, when low doses of cytoplasmic DNA are used. This finding repositions length as the predominant factor governing the discrimination between self‐ and non‐self‐cytoplasmic DNA.
See also: S Luecke et al (October 2017)
A study in this issue describes that the detection of cytoplasmic dsDNA by the immune sensor cGAS is more effective for longer fragments, suggesting that length is the predominant factor governing the discrimination between self and non‐self DNA.
- © 2017 The Author
- Salmonella ubiquitination: ARIH1 enters the fray
Ubiquitination is a post‐translational modification in which ubiquitin, a 76‐amino acid polypeptide, is covalently bound to one or more lysines of a target protein. Ubiquitination is mediated by the coordinated activity of ubiquitin activating (E1), conjugating (E2), and ligating (E3) enzymes. Ubiquitin is widely investigated for its ability to regulate key biological processes in the cell, including protein degradation and host–bacteria interactions. The determinants underlying bacterial ubiquitination, and their precise roles in host defense, have not been fully resolved. In this issue of EMBO Reports, Polajnar et al [1] discover that Ring‐between‐Ring (RBR) E3 ligase ARIH1 (also known as HHARI) is involved in formation of the ubiquitin coat surrounding cytosolic Salmonella. Evidence suggests that ARIH1, in cooperation with E3 ligases LRSAM1 and HOIP, modulates the recognition of intracellular bacteria for cell‐autonomous immunity.
See also: M Polajnar et al (September 2017)
A study in this issue describes that the Ring‐between‐Ring E3 ligase ARIH1 is involved in the formation of the ubiquitin coat surrounding cytosolic Salmonella, suggesting that ARIH1 modulates the recognition of intracellular bacteria for cell‐autonomous immunity.
- © 2017 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- cGAS is activated by DNA in a length‐dependent manner
- Stefanie Luecke1,
- Andreas Holleufer2,
- Maria H Christensen1,
- Kasper L Jønsson1,
- Gerardo A Boni1,
- Lambert K Sørensen3,
- Mogens Johannsen3,
- Martin R Jakobsen1,
- Rune Hartmann2 and
- Søren R Paludan (srp{at}biomed.au.dk)*,1
- 1Department of Biomedicine, Aarhus University, Aarhus, Denmark
- 2Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark
- 3Department of Forensic Medicine, Aarhus University Hospital, Aarhus, Denmark
- ↵*Corresponding author. Tel: +45 87167843; E‐mail: srp{at}biomed.au.dk
Cytosolic DNA stimulates innate immunity via cGAS‐STING signaling. The response to dsDNA depends on DNA length at physiological DNA concentrations. Activation of cGAS occurs more efficiently with long DNA. This preference is an intrinsic property of cGAS.
Synopsis
Cytosolic DNA stimulates innate immunity via cGAS‐STING signaling. The response to dsDNA depends on DNA length at physiological DNA concentrations. Activation of cGAS occurs more efficiently with long DNA. This preference is an intrinsic property of cGAS.
cGAS‐mediated type I IFN production is dependent on DNA length.
The length‐dependency is seen at low DNA concentrations comparable with infections.
Recombinant human cGAS produces cGAMP in a DNA length‐dependent manner in vitro.
EMBO Reports (2017) 18: 1707–1715
- Received February 2, 2017.
- Revision received July 14, 2017.
- Accepted July 18, 2017.
- © 2017 The Authors
- Expanding the host cell ubiquitylation machinery targeting cytosolic Salmonella
- Mira Polajnar1,2,3,
- Marina S Dietz4,
- Mike Heilemann4 and
- Christian Behrends (christian.behrends{at}mail03.med.uni-muenchen.de)*,1,3
- 1Institute of Biochemistry II, Goethe University School of Medicine, Frankfurt am Main, Germany
- 2German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany
- 3Munich Cluster for Systems Neurology (SyNergy), Medical Faculty, Ludwig‐Maximilians‐University München, München, Germany
- 4Institute of Physical and Theoretical Chemistry, Goethe University, Frankfurt am Main, Germany
- ↵*Corresponding author. Tel: +49 89 440046509; E‐mail: christian.behrends{at}mail03.med.uni-muenchen.de
ARIH1 contributes to the formation of an ubiquitin coat on cytosolic S. Typhimurium. Together with LRSAM1 and HOIP, ARIH1 forms a network of E3 ligases that recognize cytosolic bacteria and mediate xenophagic degradation and host immune response.
Synopsis
ARIH1 contributes to the formation of an ubiquitin coat on cytosolic S. Typhimurium. Together with LRSAM1 and HOIP, ARIH1 forms a network of E3 ligases that recognize cytosolic bacteria and mediate xenophagic degradation and host immune response.
ARIH1 ubiquitylates cytosolic S. Typhimurium and contributes K48‐linked polyubiquitin chains to the bacterial ubiquitin coat.
ARIH1 is recruited to S. Typhimurium where it colocalizes with LRSAM1.
ARIH1 and LRSAM1 have xenophagy‐dependent and ‐independent functions.
ARIH1 and LRSAM1 depletion is compensated by the recruitment of M1‐linked polyubiquitin chains to cytosolic bacteria.
ARIH1, LRSAM1 and HOIP constitute a regulatory anti‐bacterial network.
EMBO Reports (2017) 18: 1572–1585
- Received December 21, 2016.
- Revision received June 26, 2017.
- Accepted June 30, 2017.
- © 2017 The Authors
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