The common HAQ STING variant impairs cGAS-dependent antibacterial responses and is associated with susceptibility to Legionnaires’ disease in humans
The cyclic GMP-AMP synthase (cGAS)-STING pathway is central for innate immune sensing of various bacterial, viral and protozoal infections. Recent studies identified the common HAQ and R232H alleles of TMEM173/STING, but the functional consequences of these variants for primary infections are unknow...
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| Published in: | PLoS pathogens Vol. 14; no. 1; p. e1006829 |
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| Main Authors: | , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
Public Library of Science
01.01.2018
Public Library of Science (PLoS) |
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| ISSN: | 1553-7374, 1553-7366, 1553-7374 |
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| Abstract | The cyclic GMP-AMP synthase (cGAS)-STING pathway is central for innate immune sensing of various bacterial, viral and protozoal infections. Recent studies identified the common HAQ and R232H alleles of TMEM173/STING, but the functional consequences of these variants for primary infections are unknown. Here we demonstrate that cGAS- and STING-deficient murine macrophages as well as human cells of individuals carrying HAQ TMEM173/STING were severely impaired in producing type I IFNs and pro-inflammatory cytokines in response to Legionella pneumophila, bacterial DNA or cyclic dinucleotides (CDNs). In contrast, R232H attenuated cytokine production only following stimulation with bacterial CDN, but not in response to L. pneumophila or DNA. In a mouse model of Legionnaires' disease, cGAS- and STING-deficient animals exhibited higher bacterial loads as compared to wild-type mice. Moreover, the haplotype frequency of HAQ TMEM173/STING, but not of R232H TMEM173/STING, was increased in two independent cohorts of human Legionnaires' disease patients as compared to healthy controls. Our study reveals that the cGAS-STING cascade contributes to antibacterial defense against L. pneumophila in mice and men, and provides important insight into how the common HAQ TMEM173/STING variant affects antimicrobial immune responses and susceptibility to infection.
ClinicalTrials.gov DRKS00005274, German Clinical Trials Register. |
|---|---|
| AbstractList | The cyclic GMP-AMP synthase (cGAS)-STING pathway is central for innate immune sensing of various bacterial, viral and protozoal infections. Recent studies identified the common HAQ and R232H alleles of TMEM173/STING, but the functional consequences of these variants for primary infections are unknown. Here we demonstrate that cGAS- and STING-deficient murine macrophages as well as human cells of individuals carrying HAQ TMEM173/STING were severely impaired in producing type I IFNs and pro-inflammatory cytokines in response to Legionella pneumophila, bacterial DNA or cyclic dinucleotides (CDNs). In contrast, R232H attenuated cytokine production only following stimulation with bacterial CDN, but not in response to L. pneumophila or DNA. In a mouse model of Legionnaires’ disease, cGAS- and STING-deficient animals exhibited higher bacterial loads as compared to wild-type mice. Moreover, the haplotype frequency of HAQ TMEM173/STING, but not of R232H TMEM173/STING, was increased in two independent cohorts of human Legionnaires’ disease patients as compared to healthy controls. Our study reveals that the cGAS-STING cascade contributes to antibacterial defense against L. pneumophila in mice and men, and provides important insight into how the common HAQ TMEM173/STING variant affects antimicrobial immune responses and susceptibility to infection.
Trial registration
ClinicalTrials.gov DRKS00005274, German Clinical Trials Register The cyclic GMP-AMP synthase (cGAS)-STING pathway is central for innate immune sensing of various bacterial, viral and protozoal infections. Recent studies identified the common HAQ and R232H alleles of TMEM173/STING, but the functional consequences of these variants for primary infections are unknown. Here we demonstrate that cGAS- and STING-deficient murine macrophages as well as human cells of individuals carrying HAQ TMEM173/STING were severely impaired in producing type I IFNs and pro-inflammatory cytokines in response to Legionella pneumophila, bacterial DNA or cyclic dinucleotides (CDNs). In contrast, R232H attenuated cytokine production only following stimulation with bacterial CDN, but not in response to L. pneumophila or DNA. In a mouse model of Legionnaires' disease, cGAS- and STING-deficient animals exhibited higher bacterial loads as compared to wild-type mice. Moreover, the haplotype frequency of HAQ TMEM173/STING, but not of R232H TMEM173/STING, was increased in two independent cohorts of human Legionnaires' disease patients as compared to healthy controls. Our study reveals that the cGAS-STING cascade contributes to antibacterial defense against L. pneumophila in mice and men, and provides important insight into how the common HAQ TMEM173/STING variant affects antimicrobial immune responses and susceptibility to infection. Trial registration ClinicalTrials.gov DRKS00005274, German Clinical Trials Register The cyclic GMP-AMP synthase (cGAS)-STING pathway is central for innate immune sensing of various bacterial, viral and protozoal infections. Recent studies identified the common HAQ and R232H alleles of TMEM173/STING, but the functional consequences of these variants for primary infections are unknown. Here we demonstrate that cGAS- and STING-deficient murine macrophages as well as human cells of individuals carrying HAQ TMEM173/STING were severely impaired in producing type I IFNs and pro-inflammatory cytokines in response to Legionella pneumophila, bacterial DNA or cyclic dinucleotides (CDNs). In contrast, R232H attenuated cytokine production only following stimulation with bacterial CDN, but not in response to L. pneumophila or DNA. In a mouse model of Legionnaires' disease, cGAS- and STING-deficient animals exhibited higher bacterial loads as compared to wild-type mice. Moreover, the haplotype frequency of HAQ TMEM173/STING, but not of R232H TMEM173/STING, was increased in two independent cohorts of human Legionnaires' disease patients as compared to healthy controls. Our study reveals that the cGAS-STING cascade contributes to antibacterial defense against L. pneumophila in mice and men, and provides important insight into how the common HAQ TMEM173/STING variant affects antimicrobial immune responses and susceptibility to infection. ClinicalTrials.gov DRKS00005274, German Clinical Trials Register. The cyclic GMP-AMP synthase (cGAS)-STING pathway is central for innate immune sensing of various bacterial, viral and protozoal infections. Recent studies identified the common HAQ and R232H alleles of TMEM173/STING, but the functional consequences of these variants for primary infections are unknown. Here we demonstrate that cGAS- and STING-deficient murine macrophages as well as human cells of individuals carrying HAQ TMEM173/STING were severely impaired in producing type I IFNs and pro-inflammatory cytokines in response to Legionella pneumophila, bacterial DNA or cyclic dinucleotides (CDNs). In contrast, R232H attenuated cytokine production only following stimulation with bacterial CDN, but not in response to L. pneumophila or DNA. In a mouse model of Legionnaires' disease, cGAS- and STING-deficient animals exhibited higher bacterial loads as compared to wild-type mice. Moreover, the haplotype frequency of HAQ TMEM173/STING, but not of R232H TMEM173/STING, was increased in two independent cohorts of human Legionnaires' disease patients as compared to healthy controls. Our study reveals that the cGAS-STING cascade contributes to antibacterial defense against L. pneumophila in mice and men, and provides important insight into how the common HAQ TMEM173/STING variant affects antimicrobial immune responses and susceptibility to infection. The cyclic GMP-AMP synthase (cGAS)-STING pathway is central for innate immune sensing of various bacterial, viral and protozoal infections. Recent studies identified the common HAQ and R232H alleles of TMEM173/STING, but the functional consequences of these variants for primary infections are unknown. Here we demonstrate that cGAS- and STING-deficient murine macrophages as well as human cells of individuals carrying HAQ TMEM173/STING were severely impaired in producing type I IFNs and pro-inflammatory cytokines in response to Legionella pneumophila, bacterial DNA or cyclic dinucleotides (CDNs). In contrast, R232H attenuated cytokine production only following stimulation with bacterial CDN, but not in response to L. pneumophila or DNA. In a mouse model of Legionnaires' disease, cGAS- and STING-deficient animals exhibited higher bacterial loads as compared to wild-type mice. Moreover, the haplotype frequency of HAQ TMEM173/STING, but not of R232H TMEM173/STING, was increased in two independent cohorts of human Legionnaires' disease patients as compared to healthy controls. Our study reveals that the cGAS-STING cascade contributes to antibacterial defense against L. pneumophila in mice and men, and provides important insight into how the common HAQ TMEM173/STING variant affects antimicrobial immune responses and susceptibility to infection.Trial registrationClinicalTrials.gov DRKS00005274, German Clinical Trials Register. The cyclic GMP-AMP synthase (cGAS)-STING pathway is central for innate immune sensing of various bacterial, viral and protozoal infections. Recent studies identified the common HAQ and R232H alleles of TMEM173/STING, but the functional consequences of these variants for primary infections are unknown. Here we demonstrate that cGAS- and STING-deficient murine macrophages as well as human cells of individuals carrying HAQ TMEM173/STING were severely impaired in producing type I IFNs and pro-inflammatory cytokines in response to Legionella pneumophila, bacterial DNA or cyclic dinucleotides (CDNs). In contrast, R232H attenuated cytokine production only following stimulation with bacterial CDN, but not in response to L. pneumophila or DNA. In a mouse model of Legionnaires’ disease, cGAS- and STING-deficient animals exhibited higher bacterial loads as compared to wild-type mice. Moreover, the haplotype frequency of HAQ TMEM173/STING, but not of R232H TMEM173/STING, was increased in two independent cohorts of human Legionnaires’ disease patients as compared to healthy controls. Our study reveals that the cGAS-STING cascade contributes to antibacterial defense against L. pneumophila in mice and men, and provides important insight into how the common HAQ TMEM173/STING variant affects antimicrobial immune responses and susceptibility to infection. Interferons (IFNs) and pro-inflammatory cytokines are key regulators of gene expression and antibacterial defense during Legionella pneumophila infection. Here we demonstrate that production of these mediators was largely or partly dependent on the cyclic GMP-AMP synthase (cGAS)-STING pathway in human and murine cells. Cells of individuals carrying the common HAQ allele of TMEM173/STING were strongly impaired in their ability to respond to L. pneumophila, bacterial DNA or cyclic dinucleotides (CDNs), whereas the R232H allele was only attenuated in sensing of exogenous CDNs. Importantly, cGAS and STING contributed to antibacterial defense in mice during L. pneumophila lung infection, and the allele frequency of HAQ TMEM173/STING, but not of R232H TMEM173/STING, was increased in two independent cohorts of human Legionnaires’ disease patients as compared to healthy controls. Hence, sensing of bacterial DNA by the cGAS/STING pathway contributes to antibacterial defense against L. pneumophila infection, and the hypomorphic variant HAQ TMEM173/STING is associated with increased susceptibility to Legionnaires’ disease in humans. The cyclic GMP-AMP synthase (cGAS)-STING pathway is central for innate immune sensing of various bacterial, viral and protozoal infections. Recent studies identified the common HAQ and R232H alleles of TMEM173/STING, but the functional consequences of these variants for primary infections are unknown. Here we demonstrate that cGAS- and STING-deficient murine macrophages as well as human cells of individuals carrying HAQ TMEM173/STING were severely impaired in producing type I IFNs and pro-inflammatory cytokines in response to Legionella pneumophila, bacterial DNA or cyclic dinucleotides (CDNs). In contrast, R232H attenuated cytokine production only following stimulation with bacterial CDN, but not in response to L. pneumophila or DNA. In a mouse model of Legionnaires' disease, cGAS- and STING-deficient animals exhibited higher bacterial loads as compared to wild-type mice. Moreover, the haplotype frequency of HAQ TMEM173/STING, but not of R232H TMEM173/STING, was increased in two independent cohorts of human Legionnaires' disease patients as compared to healthy controls. Our study reveals that the cGAS-STING cascade contributes to antibacterial defense against L. pneumophila in mice and men, and provides important insight into how the common HAQ TMEM173/STING variant affects antimicrobial immune responses and susceptibility to infection.The cyclic GMP-AMP synthase (cGAS)-STING pathway is central for innate immune sensing of various bacterial, viral and protozoal infections. Recent studies identified the common HAQ and R232H alleles of TMEM173/STING, but the functional consequences of these variants for primary infections are unknown. Here we demonstrate that cGAS- and STING-deficient murine macrophages as well as human cells of individuals carrying HAQ TMEM173/STING were severely impaired in producing type I IFNs and pro-inflammatory cytokines in response to Legionella pneumophila, bacterial DNA or cyclic dinucleotides (CDNs). In contrast, R232H attenuated cytokine production only following stimulation with bacterial CDN, but not in response to L. pneumophila or DNA. In a mouse model of Legionnaires' disease, cGAS- and STING-deficient animals exhibited higher bacterial loads as compared to wild-type mice. Moreover, the haplotype frequency of HAQ TMEM173/STING, but not of R232H TMEM173/STING, was increased in two independent cohorts of human Legionnaires' disease patients as compared to healthy controls. Our study reveals that the cGAS-STING cascade contributes to antibacterial defense against L. pneumophila in mice and men, and provides important insight into how the common HAQ TMEM173/STING variant affects antimicrobial immune responses and susceptibility to infection.ClinicalTrials.gov DRKS00005274, German Clinical Trials Register.TRIAL REGISTRATIONClinicalTrials.gov DRKS00005274, German Clinical Trials Register. |
| Audience | Academic |
| Author | Shah, Javeed A. Opitz, Bastian Verbon, Annelies Puzianowska-Kuznicka, Monika Witzenrath, Martin Suttorp, Norbert Hamann, Lutz Naujoks, Jan Sander, Leif E. Hawn, Thomas R. Cambier, John C. Schumann, Ralf R. Jin, Lei Mockenhaupt, Frank P. Ruiz-Moreno, Juan S. |
| AuthorAffiliation | 4 VA Puget Sound Health Care System, Seattle, Washington, United states of America 7 Department of Human Epigenetics, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland 12 Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University of Florida, Gainesville, Florida, United States of America 3 Department of Medicine, University of Washington, Seattle, Washington, United states of America 8 Department of Geriatrics and Gerontology, Medical Centre of Postgraduate Education, Warsaw, Poland 1 Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany University of São Paulo FMRP/USP, BRAZIL 10 CAPNETZ STIFTUNG, Hannover, Germany 9 German Center for Lung Research (DZL), Germany 6 Institute of Tropical Medicine and International Health, Charité - Universitätsmedizi |
| AuthorAffiliation_xml | – name: 10 CAPNETZ STIFTUNG, Hannover, Germany – name: 12 Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University of Florida, Gainesville, Florida, United States of America – name: 1 Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany – name: 2 Institute of Microbiology and Hygiene, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health Berlin, Berlin, Germany – name: 6 Institute of Tropical Medicine and International Health, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany – name: 5 Department of Medical Microbiology and Infectious diseases, Erasmus University Medical Center, Rotterdam, The Netherlands – name: 7 Department of Human Epigenetics, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland – name: 4 VA Puget Sound Health Care System, Seattle, Washington, United states of America – name: 3 Department of Medicine, University of Washington, Seattle, Washington, United states of America – name: University of São Paulo FMRP/USP, BRAZIL – name: 9 German Center for Lung Research (DZL), Germany – name: 8 Department of Geriatrics and Gerontology, Medical Centre of Postgraduate Education, Warsaw, Poland – name: 11 Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, United States of America |
| Author_xml | – sequence: 1 givenname: Juan S. orcidid: 0000-0002-4661-7802 surname: Ruiz-Moreno fullname: Ruiz-Moreno, Juan S. – sequence: 2 givenname: Lutz surname: Hamann fullname: Hamann, Lutz – sequence: 3 givenname: Javeed A. orcidid: 0000-0002-2997-7988 surname: Shah fullname: Shah, Javeed A. – sequence: 4 givenname: Annelies surname: Verbon fullname: Verbon, Annelies – sequence: 5 givenname: Frank P. surname: Mockenhaupt fullname: Mockenhaupt, Frank P. – sequence: 6 givenname: Monika surname: Puzianowska-Kuznicka fullname: Puzianowska-Kuznicka, Monika – sequence: 7 givenname: Jan surname: Naujoks fullname: Naujoks, Jan – sequence: 8 givenname: Leif E. surname: Sander fullname: Sander, Leif E. – sequence: 9 givenname: Martin surname: Witzenrath fullname: Witzenrath, Martin – sequence: 10 givenname: John C. orcidid: 0000-0002-7803-242X surname: Cambier fullname: Cambier, John C. – sequence: 11 givenname: Norbert orcidid: 0000-0002-3958-1151 surname: Suttorp fullname: Suttorp, Norbert – sequence: 12 givenname: Ralf R. surname: Schumann fullname: Schumann, Ralf R. – sequence: 13 givenname: Lei orcidid: 0000-0001-6836-1142 surname: Jin fullname: Jin, Lei – sequence: 14 givenname: Thomas R. surname: Hawn fullname: Hawn, Thomas R. – sequence: 15 givenname: Bastian orcidid: 0000-0003-1276-836X surname: Opitz fullname: Opitz, Bastian |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29298342$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.4049/jimmunol.1302718 10.1038/ni.2284 10.1371/journal.ppat.1005691 10.1016/S1473-3099(05)01308-3 10.1016/j.immuni.2005.12.003 10.1126/science.1232458 10.4049/jimmunol.1100088 10.1016/j.chom.2015.05.005 10.1038/ni.1941 10.1111/j.1462-5822.2008.01232.x 10.1074/jbc.M604638200 10.1038/nature08476 10.1111/j.1462-5822.2011.01646.x 10.1073/pnas.1501289112 10.3201/eid0801.010176 10.1074/jbc.M111.231340 10.1128/IAI.00296-13 10.1016/S1473-3099(14)70713-3 10.1038/gene.2013.34 10.1128/IAI.64.12.5151-5160.1996 10.3201/eid0812.020035 10.1074/jbc.M109.018283 10.1371/journal.ppat.1000665 10.1371/journal.pone.0077846 10.1056/NEJMoa1312625 10.1084/jem.20031220 10.1016/j.celrep.2013.05.009 10.1086/322049 10.4049/jimmunol.1003565 10.1086/586741 10.1016/j.exger.2011.09.006 10.1093/cid/cir378 10.1007/s15010-004-3107-z 10.1038/nature07317 10.1073/pnas.1121286109 10.4049/jimmunol.173.2.1266 10.1016/j.chom.2012.03.007 10.1016/j.chom.2015.05.003 10.4049/jimmunol.176.10.6162 10.1038/nrmicro1967 10.1128/IAI.61.12.5361-5373.1993 10.1016/j.immuni.2011.05.016 10.1038/nature10429 10.4049/jimmunol.1601585 10.1371/journal.ppat.1005408 10.1016/j.micinf.2011.09.002 10.1128/mBio.00316-10 10.15252/embj.201488726 10.1126/science.1229963 10.1016/j.cyto.2008.08.015 10.1128/JVI.00037-14 10.1038/gene.2010.75 10.1146/annurev.med.59.061206.112455 10.1016/j.chom.2015.05.004 |
| ContentType | Journal Article |
| Copyright | COPYRIGHT 2018 Public Library of Science 2018 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Ruiz-Moreno JS, Hamann L, Shah JA, Verbon A, Mockenhaupt FP, Puzianowska-Kuznicka M, et al. (2018) The common HAQ STING variant impairs cGAS-dependent antibacterial responses and is associated with susceptibility to Legionnaires’ disease in humans. PLoS Pathog 14(1): e1006829. https://doi.org/10.1371/journal.ppat.1006829 2018 Ruiz-Moreno et al 2018 Ruiz-Moreno et al 2018 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Ruiz-Moreno JS, Hamann L, Shah JA, Verbon A, Mockenhaupt FP, Puzianowska-Kuznicka M, et al. (2018) The common HAQ STING variant impairs cGAS-dependent antibacterial responses and is associated with susceptibility to Legionnaires’ disease in humans. PLoS Pathog 14(1): e1006829. https://doi.org/10.1371/journal.ppat.1006829 |
| Copyright_xml | – notice: COPYRIGHT 2018 Public Library of Science – notice: 2018 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Ruiz-Moreno JS, Hamann L, Shah JA, Verbon A, Mockenhaupt FP, Puzianowska-Kuznicka M, et al. (2018) The common HAQ STING variant impairs cGAS-dependent antibacterial responses and is associated with susceptibility to Legionnaires’ disease in humans. PLoS Pathog 14(1): e1006829. https://doi.org/10.1371/journal.ppat.1006829 – notice: 2018 Ruiz-Moreno et al 2018 Ruiz-Moreno et al – notice: 2018 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Ruiz-Moreno JS, Hamann L, Shah JA, Verbon A, Mockenhaupt FP, Puzianowska-Kuznicka M, et al. (2018) The common HAQ STING variant impairs cGAS-dependent antibacterial responses and is associated with susceptibility to Legionnaires’ disease in humans. PLoS Pathog 14(1): e1006829. https://doi.org/10.1371/journal.ppat.1006829 |
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| DOI | 10.1371/journal.ppat.1006829 |
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| Language | English |
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| Notes | new_version ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Article-2 ObjectType-Feature-1 content type line 23 The authors have declared that no competing interests exist. Membership of the CAPNETZ Study Group is provided in the Acknowledgments. |
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| References | JW Den Boer (ref35) 2002; 8 R Sporri (ref6) 2006; 176 G Schiavoni (ref7) 2004; 173 DB Stetson (ref13) 2006; 24 J Wu (ref21) 2013; 339 R Wassermann (ref24) 2015; 17 P Bledowski (ref55) 2011; 46 S LeibundGut-Landmann (ref10) 2011; 186 AS Brown (ref16) 2016; 12 H von Baum (ref2) 2008; 46 J Lippmann (ref14) 2008; 10 J Fu (ref32) 2015; 7 AK Mankan (ref33) 2014; 33 N Yan (ref44) 2010; 11 G Yi (ref28) 2013; 8 L Jin (ref27) 2011; 12 M Levet-Paulo (ref47) 2011; 286 T Welte (ref54) 2004; 32 KM Monroe (ref49) 2009; 5 AM Copenhaver (ref15) 2015; 112 EA Creasey (ref31) 2012; 109 L Heath (ref5) 1996; 64 PS Manzanillo (ref43) 2012; 11 TR Hawn (ref37) 2003; 198 EA Misch (ref41) 2013; 14 H Ishikawa (ref19) 2009; 461 NW Schroder (ref38) 2005; 5 L Sun (ref22) 2013; 339 H Ishikawa (ref18) 2008; 455 CR Harding (ref52) 2013; 81 Y Zhang (ref26) 2014; 193 RR Isberg (ref3) 2009; 7 HC Boshuizen (ref34) 2001; 184 J Naujoks (ref12) 2016; 12 B Opitz (ref8) 2006; 281 L Jin (ref53) 2011; 187 RO Watson (ref23) 2015; 17 S Patel (ref29) 2017; 198 P Nahid (ref56) 2011; 53 MG Netea (ref39) 2012; 13 M Fujita (ref11) 2008; 44 AC Collins (ref25) 2015; 17 Y Liu (ref42) 2014; 371 DL Burdette (ref20) 2011; 478 EJ Diner (ref30) 2013; 3 S Garantziotis (ref40) 2008; 59 A Levi (ref46) 2011; 2 AB Sadosky (ref51) 1993; 61 T Abe (ref50) 2014; 88 J Naujoks (ref9) 2017 CR Plumlee (ref48) 2009; 284 KD Lettinga (ref36) 2002; 8 AA Abdul-Sater (ref17) 2012; 14 N Phin (ref1) 2014; 14 S Sharma (ref45) 2011; 35 J Lippmann (ref4) 2011; 13 |
| References_xml | – volume: 193 start-page: 2394 year: 2014 ident: ref26 article-title: The DNA sensor, cyclic GMP-AMP synthase, is essential for induction of IFN-beta during Chlamydia trachomatis infection publication-title: J Immunol doi: 10.4049/jimmunol.1302718 – volume: 13 start-page: 535 year: 2012 ident: ref39 article-title: Genetic variation in Toll-like receptors and disease susceptibility publication-title: Nat Immunol doi: 10.1038/ni.2284 – volume: 12 start-page: e1005691 year: 2016 ident: ref16 article-title: Cooperation between Monocyte-Derived Cells and Lymphoid Cells in the Acute Response to a Bacterial Lung Pathogen publication-title: PLoS Pathog doi: 10.1371/journal.ppat.1005691 – volume: 5 start-page: 156 year: 2005 ident: ref38 article-title: Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious disease publication-title: Lancet Infect Dis doi: 10.1016/S1473-3099(05)01308-3 – volume: 24 start-page: 93 year: 2006 ident: ref13 article-title: Recognition of cytosolic DNA activates an IRF3-dependent innate immune response publication-title: Immunity doi: 10.1016/j.immuni.2005.12.003 – volume: 339 start-page: 786 year: 2013 ident: ref22 article-title: Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway publication-title: Science doi: 10.1126/science.1232458 – volume: 187 start-page: 2595 year: 2011 ident: ref53 article-title: MPYS is required for IFN response factor 3 activation and type I IFN production in the response of cultured phagocytes to bacterial second messengers cyclic-di-AMP and cyclic-di-GMP publication-title: J Immunol doi: 10.4049/jimmunol.1100088 – volume: 17 start-page: 820 year: 2015 ident: ref25 article-title: Cyclic GMP-AMP Synthase Is an Innate Immune DNA Sensor for Mycobacterium tuberculosis publication-title: Cell Host Microbe doi: 10.1016/j.chom.2015.05.005 – volume: 11 start-page: 1005 year: 2010 ident: ref44 article-title: The cytosolic exonuclease TREX1 inhibits the innate immune response to human immunodeficiency virus type 1 publication-title: Nat Immunol doi: 10.1038/ni.1941 – volume: 10 start-page: 2579 year: 2008 ident: ref14 article-title: IFNbeta responses induced by intracellular bacteria or cytosolic DNA in different human cells do not require ZBP1 (DLM-1/DAI) publication-title: Cell Microbiol doi: 10.1111/j.1462-5822.2008.01232.x – volume: 281 start-page: 36173 year: 2006 ident: ref8 article-title: Legionella pneumophila induces IFNbeta in lung epithelial cells via IPS-1 and IRF3, which also control bacterial replication publication-title: J Biol Chem doi: 10.1074/jbc.M604638200 – volume: 461 start-page: 788 year: 2009 ident: ref19 article-title: STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity publication-title: Nature doi: 10.1038/nature08476 – volume: 13 start-page: 1668 year: 2011 ident: ref4 article-title: Dissection of a type I interferon pathway in controlling bacterial intracellular infection in mice publication-title: Cell Microbiol doi: 10.1111/j.1462-5822.2011.01646.x – volume: 112 start-page: 7557 year: 2015 ident: ref15 article-title: IL-1R signaling enables bystander cells to overcome bacterial blockade of host protein synthesis publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.1501289112 – volume: 8 start-page: 37 year: 2002 ident: ref35 article-title: A large outbreak of Legionnaires’ disease at a flower show, the Netherlands, 1999 publication-title: Emerg Infect Dis doi: 10.3201/eid0801.010176 – volume: 286 start-page: 31136 year: 2011 ident: ref47 article-title: The atypical two-component sensor kinase Lpl0330 from Legionella pneumophila controls the bifunctional diguanylate cyclase-phosphodiesterase Lpl0329 to modulate bis-(3’-5’)-cyclic dimeric GMP synthesis publication-title: J Biol Chem doi: 10.1074/jbc.M111.231340 – volume: 81 start-page: 2598 year: 2013 ident: ref52 article-title: The Dot/Icm effector SdhA is necessary for virulence of Legionella pneumophila in Galleria mellonella and A/J mice publication-title: Infect Immun doi: 10.1128/IAI.00296-13 – volume: 14 start-page: 1011 year: 2014 ident: ref1 article-title: Epidemiology and clinical management of Legionnaires’ disease publication-title: Lancet Infect Dis doi: 10.1016/S1473-3099(14)70713-3 – volume: 14 start-page: 420 year: 2013 ident: ref41 article-title: A TLR6 polymorphism is associated with increased risk of Legionnaires’ disease publication-title: Genes Immun doi: 10.1038/gene.2013.34 – volume: 64 start-page: 5151 year: 1996 ident: ref5 article-title: Effector mechanisms responsible for gamma interferon-mediated host resistance to Legionella pneumophila lung infection: the role of endogenous nitric oxide differs in susceptible and resistant murine hosts publication-title: Infect Immun doi: 10.1128/IAI.64.12.5151-5160.1996 – volume: 8 start-page: 1448 year: 2002 ident: ref36 article-title: Legionnaires’ disease at a Dutch flower show: prognostic factors and impact of therapy publication-title: Emerg Infect Dis doi: 10.3201/eid0812.020035 – volume: 284 start-page: 30058 year: 2009 ident: ref48 article-title: Interferons direct an effective innate response to Legionella pneumophila infection publication-title: J Biol Chem doi: 10.1074/jbc.M109.018283 – volume: 5 start-page: e1000665 year: 2009 ident: ref49 article-title: Identification of host cytosolic sensors and bacterial factors regulating the type I interferon response to Legionella pneumophila publication-title: PLoS Pathog doi: 10.1371/journal.ppat.1000665 – volume: 8 start-page: e77846 year: 2013 ident: ref28 article-title: Single nucleotide polymorphisms of human STING can affect innate immune response to cyclic dinucleotides publication-title: PLoS One doi: 10.1371/journal.pone.0077846 – volume: 371 start-page: 507 year: 2014 ident: ref42 article-title: Activated STING in a vascular and pulmonary syndrome publication-title: N Engl J Med doi: 10.1056/NEJMoa1312625 – volume: 198 start-page: 1563 year: 2003 ident: ref37 article-title: A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires’ disease publication-title: J Exp Med doi: 10.1084/jem.20031220 – volume: 3 start-page: 1355 year: 2013 ident: ref30 article-title: The innate immune DNA sensor cGAS produces a noncanonical cyclic dinucleotide that activates human STING publication-title: Cell Rep doi: 10.1016/j.celrep.2013.05.009 – volume: 184 start-page: 515 year: 2001 ident: ref34 article-title: Subclinical Legionella infection in workers near the source of a large outbreak of Legionnaires disease publication-title: J Infect Dis doi: 10.1086/322049 – volume: 186 start-page: 3130 year: 2011 ident: ref10 article-title: Nonhematopoietic cells are key players in innate control of bacterial airway infection publication-title: J Immunol doi: 10.4049/jimmunol.1003565 – volume: 46 start-page: 1356 year: 2008 ident: ref2 article-title: Community-acquired Legionella pneumonia: new insights from the German competence network for community acquired pneumonia publication-title: Clin Infect Dis doi: 10.1086/586741 – volume: 46 start-page: 1003 year: 2011 ident: ref55 article-title: Medical, psychological and socioeconomic aspects of aging in Poland: assumptions and objectives of the PolSenior project publication-title: Exp Gerontol doi: 10.1016/j.exger.2011.09.006 – volume: 53 start-page: 291 year: 2011 ident: ref56 article-title: Racial differences in tuberculosis infection in United States communities: the coronary artery risk development in young adults study publication-title: Clin Infect Dis doi: 10.1093/cid/cir378 – volume: 32 start-page: 234 year: 2004 ident: ref54 article-title: CAPNETZ-community-acquired pneumonia competence network publication-title: Infection doi: 10.1007/s15010-004-3107-z – volume: 455 start-page: 674 year: 2008 ident: ref18 article-title: STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling publication-title: Nature doi: 10.1038/nature07317 – volume: 7 year: 2015 ident: ref32 article-title: STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade publication-title: Sci Transl Med – volume: 109 start-page: 3481 year: 2012 ident: ref31 article-title: The protein SdhA maintains the integrity of the Legionella-containing vacuole publication-title: Proc Natl Acad Sci U S A doi: 10.1073/pnas.1121286109 – volume: 173 start-page: 1266 year: 2004 ident: ref7 article-title: Type I IFN protects permissive macrophages from Legionella pneumophila infection through an IFN-gamma-independent pathway publication-title: J Immunol doi: 10.4049/jimmunol.173.2.1266 – volume: 11 start-page: 469 year: 2012 ident: ref43 article-title: Mycobacterium tuberculosis activates the DNA-dependent cytosolic surveillance pathway within macrophages publication-title: Cell Host Microbe doi: 10.1016/j.chom.2012.03.007 – volume: 17 start-page: 799 year: 2015 ident: ref24 article-title: Mycobacterium tuberculosis Differentially Activates cGAS- and Inflammasome-Dependent Intracellular Immune Responses through ESX-1 publication-title: Cell Host Microbe doi: 10.1016/j.chom.2015.05.003 – volume: 176 start-page: 6162 year: 2006 ident: ref6 article-title: MyD88-dependent IFN-gamma production by NK cells is key for control of Legionella pneumophila infection publication-title: J Immunol doi: 10.4049/jimmunol.176.10.6162 – volume: 7 start-page: 13 year: 2009 ident: ref3 article-title: The Legionella pneumophila replication vacuole: making a cosy niche inside host cells publication-title: Nat Rev Microbiol doi: 10.1038/nrmicro1967 – volume: 61 start-page: 5361 year: 1993 ident: ref51 article-title: Identification of Legionella pneumophila genes required for growth within and killing of human macrophages publication-title: Infect Immun doi: 10.1128/IAI.61.12.5361-5373.1993 – volume: 35 start-page: 194 year: 2011 ident: ref45 article-title: Innate immune recognition of an AT-rich stem-loop DNA motif in the Plasmodium falciparum genome publication-title: Immunity doi: 10.1016/j.immuni.2011.05.016 – volume: 478 start-page: 515 year: 2011 ident: ref20 article-title: STING is a direct innate immune sensor of cyclic di-GMP publication-title: Nature doi: 10.1038/nature10429 – volume: 198 start-page: 776 year: 2017 ident: ref29 article-title: The Common R71H-G230A-R293Q Human TMEM173 Is a Null Allele publication-title: J Immunol doi: 10.4049/jimmunol.1601585 – volume: 12 start-page: e1005408 year: 2016 ident: ref12 article-title: IFNs Modify the Proteome of Legionella-Containing Vacuoles and Restrict Infection Via IRG1-Derived Itaconic Acid publication-title: PLoS Pathog doi: 10.1371/journal.ppat.1005408 – volume: 14 start-page: 188 year: 2012 ident: ref17 article-title: The overlapping host responses to bacterial cyclic dinucleotides publication-title: Microbes Infect doi: 10.1016/j.micinf.2011.09.002 – volume: 2 start-page: e00316 year: 2011 ident: ref46 article-title: Cyclic diguanylate signaling proteins control intracellular growth of Legionella pneumophila publication-title: MBio doi: 10.1128/mBio.00316-10 – volume: 33 start-page: 2937 year: 2014 ident: ref33 article-title: Cytosolic RNA:DNA hybrids activate the cGAS-STING axis publication-title: EMBO J doi: 10.15252/embj.201488726 – volume: 339 start-page: 826 year: 2013 ident: ref21 article-title: Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA publication-title: Science doi: 10.1126/science.1229963 – volume: 44 start-page: 298 year: 2008 ident: ref11 article-title: TNF receptor 1 and 2 contribute in different ways to resistance to Legionella pneumophila-induced mortality in mice publication-title: Cytokine doi: 10.1016/j.cyto.2008.08.015 – volume: 88 start-page: 5328 year: 2014 ident: ref50 article-title: Cytosolic-DNA-mediated, STING-dependent proinflammatory gene induction necessitates canonical NF-kappaB activation through TBK1 publication-title: J Virol doi: 10.1128/JVI.00037-14 – volume: 12 start-page: 263 year: 2011 ident: ref27 article-title: Identification and characterization of a loss-of-function human MPYS variant publication-title: Genes Immun doi: 10.1038/gene.2010.75 – year: 2017 ident: ref9 article-title: Innate sensing and cell-autonomous resistance pathways in Legionella pneumophila infection publication-title: Int J Med Microbiol – volume: 59 start-page: 343 year: 2008 ident: ref40 article-title: The effect of toll-like receptors and toll-like receptor genetics in human disease publication-title: Annu Rev Med doi: 10.1146/annurev.med.59.061206.112455 – volume: 17 start-page: 811 year: 2015 ident: ref23 article-title: The Cytosolic Sensor cGAS Detects Mycobacterium tuberculosis DNA to Induce Type I Interferons and Activate Autophagy publication-title: Cell Host Microbe doi: 10.1016/j.chom.2015.05.004 |
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| SubjectTerms | Adult Aged Aged, 80 and over AMP Analysis Animal diseases Animals Anti-Bacterial Agents - therapeutic use Antibacterial agents Antiinfectives and antibacterials Bacteria Biology and Life Sciences Case-Control Studies Cells, Cultured Clinical trials Cyclic GMP Cytokines Deoxyribonucleic acid Disease control Disease susceptibility DNA Female Gene expression Genetic Predisposition to Disease Haplotypes Health aspects HEK293 Cells Humans Immune response Immunity, Innate - drug effects Immunity, Innate - genetics Infection Infections Infectious diseases Inflammation Internal medicine Kinases Legionella Legionella pneumophila - immunology Legionnaire's disease Legionnaires' disease Legionnaires' Disease - drug therapy Legionnaires' Disease - genetics Legionnaires' disease bacterium Macrophages Male Medical research Medicine Medicine and Health Sciences Membrane Proteins - genetics Mice Mice, Inbred C57BL Middle Aged Nucleotidyltransferases - physiology Polymorphism, Genetic Research and Analysis Methods Treatment Outcome Tuberculosis |
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| Title | The common HAQ STING variant impairs cGAS-dependent antibacterial responses and is associated with susceptibility to Legionnaires’ disease in humans |
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