Clinical isolates of the modern Mycobacterium tuberculosis lineage 4 evade host defense in human macrophages through eluding IL-1β-induced autophagy View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-05-24

AUTHORS

Alessandra Romagnoli, Elisa Petruccioli, Ivana Palucci, Serena Camassa, Elisabetta Carata, Linda Petrone, Stefania Mariano, Michela Sali, Luciana Dini, Enrico Girardi, Giovanni Delogu, Delia Goletti, Gian Maria Fimia

ABSTRACT

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), has infected over 1.7 billion people worldwide and causes 1.4 million deaths annually. Recently, genome sequence analysis has allowed the reconstruction of Mycobacterium tuberculosis complex (MTBC) evolution, with the identification of seven phylogeographic lineages: four referred to as evolutionarily "ancient", and three "modern". The MTBC strains belonging to "modern" lineages appear to show enhanced virulence that may have warranted improved transmission in humans over ancient lineages through molecular mechanisms that remain to be fully characterized. To evaluate the impact of MTBC genetic diversity on the innate immune response, we analyzed intracellular bacterial replication, inflammatory cytokine levels, and autophagy response in human primary macrophages infected with MTBC clinical isolates belonging to the ancient lineages 1 and 5, and the modern lineage 4. We show that, when compared to ancient lineage 1 and 5, MTBC strains belonging to modern lineage 4 show a higher rate of replication, associated to a significant production of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) and induction of a functional autophagy process. Interestingly, we found that the increased autophagic flux observed in macrophages infected with modern MTBC is due to an autocrine activity of the proinflammatory cytokine IL-1β, since autophagosome maturation is blocked by an interleukin-1 receptor antagonist. Unexpectedly, IL-1β-induced autophagy is not disadvantageous for the survival of modern Mtb strains, which reside within Rab5-positive phagosomal vesicles and avoid autophagosome engulfment. Altogether, these results suggest that autophagy triggered by inflammatory cytokines is compatible with a high rate of intracellular bacilli replication and may therefore contribute to the increased pathogenicity of the modern MTBC lineages. More... »

PAGES

624

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41419-018-0640-8

DOI

http://dx.doi.org/10.1038/s41419-018-0640-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1104158452

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29795378


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1107", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Immunology", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Autophagosomes", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Autophagy", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Host-Pathogen Interactions", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Immune Evasion", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Inflammation Mediators", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Interleukin-1beta", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Macrophages", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Mycobacterium tuberculosis", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Phylogeny", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Signal Transduction", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Department of Epidemiology and Preclinical Research, National Institutes for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, 00149 Italy", 
          "id": "http://www.grid.ac/institutes/grid.414603.4", 
          "name": [
            "Department of Epidemiology and Preclinical Research, National Institutes for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, 00149 Italy"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Romagnoli", 
        "givenName": "Alessandra", 
        "id": "sg:person.01130437467.18", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01130437467.18"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Epidemiology and Preclinical Research, National Institutes for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, 00149 Italy", 
          "id": "http://www.grid.ac/institutes/grid.414603.4", 
          "name": [
            "Department of Epidemiology and Preclinical Research, National Institutes for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, 00149 Italy"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Petruccioli", 
        "givenName": "Elisa", 
        "id": "sg:person.01316222666.31", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01316222666.31"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Institute of Microbiology, Universita\u2019 Cattolica del Sacro Cuore \u2013 Fondazione Policlinico Gemelli, Rome, 00168 Italy", 
          "id": "http://www.grid.ac/institutes/grid.411075.6", 
          "name": [
            "Institute of Microbiology, Universita\u2019 Cattolica del Sacro Cuore \u2013 Fondazione Policlinico Gemelli, Rome, 00168 Italy"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Palucci", 
        "givenName": "Ivana", 
        "id": "sg:person.01161317047.40", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01161317047.40"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Institute of Microbiology, Universita\u2019 Cattolica del Sacro Cuore \u2013 Fondazione Policlinico Gemelli, Rome, 00168 Italy", 
          "id": "http://www.grid.ac/institutes/grid.411075.6", 
          "name": [
            "Institute of Microbiology, Universita\u2019 Cattolica del Sacro Cuore \u2013 Fondazione Policlinico Gemelli, Rome, 00168 Italy"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Camassa", 
        "givenName": "Serena", 
        "id": "sg:person.01026771172.24", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01026771172.24"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, University of Salento, Lecce, 73100 Italy", 
          "id": "http://www.grid.ac/institutes/grid.9906.6", 
          "name": [
            "Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, University of Salento, Lecce, 73100 Italy"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Carata", 
        "givenName": "Elisabetta", 
        "id": "sg:person.01346531721.17", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01346531721.17"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Epidemiology and Preclinical Research, National Institutes for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, 00149 Italy", 
          "id": "http://www.grid.ac/institutes/grid.414603.4", 
          "name": [
            "Department of Epidemiology and Preclinical Research, National Institutes for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, 00149 Italy"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Petrone", 
        "givenName": "Linda", 
        "id": "sg:person.0755160366.91", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0755160366.91"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, University of Salento, Lecce, 73100 Italy", 
          "id": "http://www.grid.ac/institutes/grid.9906.6", 
          "name": [
            "Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, University of Salento, Lecce, 73100 Italy"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Mariano", 
        "givenName": "Stefania", 
        "id": "sg:person.01202453300.95", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01202453300.95"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Institute of Microbiology, Universita\u2019 Cattolica del Sacro Cuore \u2013 Fondazione Policlinico Gemelli, Rome, 00168 Italy", 
          "id": "http://www.grid.ac/institutes/grid.411075.6", 
          "name": [
            "Institute of Microbiology, Universita\u2019 Cattolica del Sacro Cuore \u2013 Fondazione Policlinico Gemelli, Rome, 00168 Italy"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Sali", 
        "givenName": "Michela", 
        "id": "sg:person.01006361171.07", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01006361171.07"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, University of Salento, Lecce, 73100 Italy", 
          "id": "http://www.grid.ac/institutes/grid.9906.6", 
          "name": [
            "Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, University of Salento, Lecce, 73100 Italy"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Dini", 
        "givenName": "Luciana", 
        "id": "sg:person.01064477442.53", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01064477442.53"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Epidemiology and Preclinical Research, National Institutes for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, 00149 Italy", 
          "id": "http://www.grid.ac/institutes/grid.414603.4", 
          "name": [
            "Department of Epidemiology and Preclinical Research, National Institutes for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, 00149 Italy"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Girardi", 
        "givenName": "Enrico", 
        "id": "sg:person.01222655205.82", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01222655205.82"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Institute of Microbiology, Universita\u2019 Cattolica del Sacro Cuore \u2013 Fondazione Policlinico Gemelli, Rome, 00168 Italy", 
          "id": "http://www.grid.ac/institutes/grid.411075.6", 
          "name": [
            "Institute of Microbiology, Universita\u2019 Cattolica del Sacro Cuore \u2013 Fondazione Policlinico Gemelli, Rome, 00168 Italy"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Delogu", 
        "givenName": "Giovanni", 
        "id": "sg:person.01367573522.56", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01367573522.56"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Epidemiology and Preclinical Research, National Institutes for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, 00149 Italy", 
          "id": "http://www.grid.ac/institutes/grid.414603.4", 
          "name": [
            "Department of Epidemiology and Preclinical Research, National Institutes for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, 00149 Italy"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Goletti", 
        "givenName": "Delia", 
        "id": "sg:person.01200446072.99", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01200446072.99"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, University of Salento, Lecce, 73100 Italy", 
          "id": "http://www.grid.ac/institutes/grid.9906.6", 
          "name": [
            "Department of Epidemiology and Preclinical Research, National Institutes for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, 00149 Italy", 
            "Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, University of Salento, Lecce, 73100 Italy"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Fimia", 
        "givenName": "Gian Maria", 
        "id": "sg:person.0741346170.03", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0741346170.03"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1038/nature16451", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033165191", 
          "https://doi.org/10.1038/nature16451"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrd.2017.162", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1091891119", 
          "https://doi.org/10.1038/nrd.2017.162"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ni.3273", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025859742", 
          "https://doi.org/10.1038/ni.3273"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s10875-014-0103-7", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025325690", 
          "https://doi.org/10.1007/s10875-014-0103-7"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature02837", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017834156", 
          "https://doi.org/10.1038/nature02837"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/ncomms11290", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010683868", 
          "https://doi.org/10.1038/ncomms11290"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/srep23089", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1043291608", 
          "https://doi.org/10.1038/srep23089"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/82_2013_332", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020601145", 
          "https://doi.org/10.1007/82_2013_332"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrmicro.2018.8", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1101104614", 
          "https://doi.org/10.1038/nrmicro.2018.8"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/mi.2011.14", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013828195", 
          "https://doi.org/10.1038/mi.2011.14"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrd4696", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002419266", 
          "https://doi.org/10.1038/nrd4696"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nri3532", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022777012", 
          "https://doi.org/10.1038/nri3532"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/srep16320", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1004656238", 
          "https://doi.org/10.1038/srep16320"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2018-05-24", 
    "datePublishedReg": "2018-05-24", 
    "description": "Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), has infected over 1.7 billion people worldwide and causes 1.4 million deaths annually. Recently, genome sequence analysis has allowed the reconstruction of Mycobacterium tuberculosis complex (MTBC) evolution, with the identification of seven phylogeographic lineages: four referred to as evolutionarily \"ancient\", and three \"modern\". The MTBC strains belonging to \"modern\" lineages appear to show enhanced virulence that may have warranted improved transmission in humans over ancient lineages through molecular mechanisms that remain to be fully characterized. To evaluate the impact of MTBC genetic diversity on the innate immune response, we analyzed intracellular bacterial replication, inflammatory cytokine levels, and autophagy response in human primary macrophages infected with MTBC clinical isolates belonging to the ancient lineages 1 and 5, and the modern lineage 4. We show that, when compared to ancient lineage 1 and 5, MTBC strains belonging to modern lineage 4 show a higher rate of replication, associated to a significant production of proinflammatory cytokines (IL-1\u03b2, IL-6, and TNF-\u03b1) and induction of a functional autophagy process. Interestingly, we found that the increased autophagic flux observed in macrophages infected with modern MTBC is due to an autocrine activity of the proinflammatory cytokine IL-1\u03b2, since autophagosome maturation is blocked by an interleukin-1 receptor antagonist. Unexpectedly, IL-1\u03b2-induced autophagy is not disadvantageous for the survival of modern Mtb strains, which reside within Rab5-positive phagosomal vesicles and avoid autophagosome engulfment. Altogether, these results suggest that autophagy triggered by inflammatory cytokines is compatible with a high rate of intracellular bacilli replication and may therefore contribute to the increased pathogenicity of the modern MTBC lineages.", 
    "genre": "article", 
    "id": "sg:pub.10.1038/s41419-018-0640-8", 
    "inLanguage": "en", 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.6853760", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1042939", 
        "issn": [
          "2041-4889"
        ], 
        "name": "Cell Death & Disease", 
        "publisher": "Springer Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "6", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "9"
      }
    ], 
    "keywords": [
      "ancient lineage 1", 
      "IL-1\u03b2", 
      "lineage 1", 
      "genome sequence analysis", 
      "intracellular bacterial replication", 
      "evade host defenses", 
      "phylogeographic lineages", 
      "ancient lineage", 
      "clinical isolates", 
      "genetic diversity", 
      "human primary macrophages", 
      "interleukin-1 receptor antagonist", 
      "proinflammatory cytokines IL-1\u03b2", 
      "MTBC genetic diversity", 
      "MTBC clinical isolates", 
      "inflammatory cytokine levels", 
      "molecular mechanisms", 
      "cytokines IL-1\u03b2", 
      "autophagy process", 
      "sequence analysis", 
      "lineages", 
      "autophagy response", 
      "innate immune response", 
      "lineage 4", 
      "autophagic flux", 
      "high rate", 
      "bacterial replication", 
      "primary macrophages", 
      "autophagy", 
      "cytokine levels", 
      "human macrophages", 
      "proinflammatory cytokines", 
      "inflammatory cytokines", 
      "receptor antagonist", 
      "immune response", 
      "autocrine activity", 
      "enhanced virulence", 
      "MTB strains", 
      "host defense", 
      "replication", 
      "MTBC lineages", 
      "Mycobacterium tuberculosis", 
      "tuberculosis", 
      "causative agent", 
      "macrophages", 
      "cytokines", 
      "MTBC", 
      "isolates", 
      "complex evolution", 
      "virulence", 
      "engulfment", 
      "diversity", 
      "vesicles", 
      "pathogenicity", 
      "significant production", 
      "antagonist", 
      "maturation", 
      "defense", 
      "response", 
      "death", 
      "induction", 
      "survival", 
      "strains", 
      "identification", 
      "rate", 
      "evolution", 
      "humans", 
      "mechanism", 
      "agents", 
      "production", 
      "activity", 
      "levels", 
      "people", 
      "transmission", 
      "reconstruction", 
      "analysis", 
      "process", 
      "impact", 
      "results", 
      "flux", 
      "Mycobacterium tuberculosis complex (MTBC) evolution", 
      "tuberculosis complex (MTBC) evolution", 
      "modern lineage 4", 
      "functional autophagy process", 
      "modern MTBC", 
      "modern Mtb strains", 
      "Rab5-positive phagosomal vesicles", 
      "phagosomal vesicles", 
      "autophagosome engulfment", 
      "intracellular bacilli replication", 
      "bacilli replication", 
      "modern MTBC lineages", 
      "modern Mycobacterium tuberculosis lineage 4 evade host defense", 
      "Mycobacterium tuberculosis lineage 4 evade host defense", 
      "tuberculosis lineage 4 evade host defense", 
      "lineage 4 evade host defense"
    ], 
    "name": "Clinical isolates of the modern Mycobacterium tuberculosis lineage 4 evade host defense in human macrophages through eluding IL-1\u03b2-induced autophagy", 
    "pagination": "624", 
    "productId": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1104158452"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/s41419-018-0640-8"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "29795378"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/s41419-018-0640-8", 
      "https://app.dimensions.ai/details/publication/pub.1104158452"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2022-01-01T18:47", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-springernature-scigraph/baseset/20220101/entities/gbq_results/article/article_766.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://doi.org/10.1038/s41419-018-0640-8"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41419-018-0640-8'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41419-018-0640-8'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41419-018-0640-8'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41419-018-0640-8'


 

This table displays all metadata directly associated to this object as RDF triples.

346 TRIPLES      22 PREDICATES      146 URIs      125 LITERALS      18 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/s41419-018-0640-8 schema:about N27234a3ec0364e529bd360720c04fb25
2 N2a178db82d6b41d7a7ea260894c51690
3 N6ecceffc0c964ea48a5d93f6ade51bf7
4 N70c250d71c9042188188b06e1945f857
5 N8761dddb99bd4b46880c16e7030f454f
6 N8f3b281dd2e34a10ab3a9a734f725f9a
7 N9e82a1e2951e4ed79f33cf3aa7fc2022
8 Nab3704d9d8d0462aaef2e5deb477d130
9 Nb4eb36bf92e54b0aadf5283c160c5eb6
10 Nbb0b5dc5f7074afc89847e2a11b54035
11 Nd56dac0d075a493dbc57dabfa106be24
12 anzsrc-for:11
13 anzsrc-for:1107
14 schema:author N1bd5c319c3264488885964fe45d05376
15 schema:citation sg:pub.10.1007/82_2013_332
16 sg:pub.10.1007/s10875-014-0103-7
17 sg:pub.10.1038/mi.2011.14
18 sg:pub.10.1038/nature02837
19 sg:pub.10.1038/nature16451
20 sg:pub.10.1038/ncomms11290
21 sg:pub.10.1038/ni.3273
22 sg:pub.10.1038/nrd.2017.162
23 sg:pub.10.1038/nrd4696
24 sg:pub.10.1038/nri3532
25 sg:pub.10.1038/nrmicro.2018.8
26 sg:pub.10.1038/srep16320
27 sg:pub.10.1038/srep23089
28 schema:datePublished 2018-05-24
29 schema:datePublishedReg 2018-05-24
30 schema:description Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), has infected over 1.7 billion people worldwide and causes 1.4 million deaths annually. Recently, genome sequence analysis has allowed the reconstruction of Mycobacterium tuberculosis complex (MTBC) evolution, with the identification of seven phylogeographic lineages: four referred to as evolutionarily "ancient", and three "modern". The MTBC strains belonging to "modern" lineages appear to show enhanced virulence that may have warranted improved transmission in humans over ancient lineages through molecular mechanisms that remain to be fully characterized. To evaluate the impact of MTBC genetic diversity on the innate immune response, we analyzed intracellular bacterial replication, inflammatory cytokine levels, and autophagy response in human primary macrophages infected with MTBC clinical isolates belonging to the ancient lineages 1 and 5, and the modern lineage 4. We show that, when compared to ancient lineage 1 and 5, MTBC strains belonging to modern lineage 4 show a higher rate of replication, associated to a significant production of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) and induction of a functional autophagy process. Interestingly, we found that the increased autophagic flux observed in macrophages infected with modern MTBC is due to an autocrine activity of the proinflammatory cytokine IL-1β, since autophagosome maturation is blocked by an interleukin-1 receptor antagonist. Unexpectedly, IL-1β-induced autophagy is not disadvantageous for the survival of modern Mtb strains, which reside within Rab5-positive phagosomal vesicles and avoid autophagosome engulfment. Altogether, these results suggest that autophagy triggered by inflammatory cytokines is compatible with a high rate of intracellular bacilli replication and may therefore contribute to the increased pathogenicity of the modern MTBC lineages.
31 schema:genre article
32 schema:inLanguage en
33 schema:isAccessibleForFree true
34 schema:isPartOf Nc30525b60a2d444985070eb354c169a6
35 Neb1961664c554e2794c39c0f3d7e622a
36 sg:journal.1042939
37 schema:keywords IL-1β
38 MTB strains
39 MTBC
40 MTBC clinical isolates
41 MTBC genetic diversity
42 MTBC lineages
43 Mycobacterium tuberculosis
44 Mycobacterium tuberculosis complex (MTBC) evolution
45 Mycobacterium tuberculosis lineage 4 evade host defense
46 Rab5-positive phagosomal vesicles
47 activity
48 agents
49 analysis
50 ancient lineage
51 ancient lineage 1
52 antagonist
53 autocrine activity
54 autophagic flux
55 autophagosome engulfment
56 autophagy
57 autophagy process
58 autophagy response
59 bacilli replication
60 bacterial replication
61 causative agent
62 clinical isolates
63 complex evolution
64 cytokine levels
65 cytokines
66 cytokines IL-1β
67 death
68 defense
69 diversity
70 engulfment
71 enhanced virulence
72 evade host defenses
73 evolution
74 flux
75 functional autophagy process
76 genetic diversity
77 genome sequence analysis
78 high rate
79 host defense
80 human macrophages
81 human primary macrophages
82 humans
83 identification
84 immune response
85 impact
86 induction
87 inflammatory cytokine levels
88 inflammatory cytokines
89 innate immune response
90 interleukin-1 receptor antagonist
91 intracellular bacilli replication
92 intracellular bacterial replication
93 isolates
94 levels
95 lineage 1
96 lineage 4
97 lineage 4 evade host defense
98 lineages
99 macrophages
100 maturation
101 mechanism
102 modern MTBC
103 modern MTBC lineages
104 modern Mtb strains
105 modern Mycobacterium tuberculosis lineage 4 evade host defense
106 modern lineage 4
107 molecular mechanisms
108 pathogenicity
109 people
110 phagosomal vesicles
111 phylogeographic lineages
112 primary macrophages
113 process
114 production
115 proinflammatory cytokines
116 proinflammatory cytokines IL-1β
117 rate
118 receptor antagonist
119 reconstruction
120 replication
121 response
122 results
123 sequence analysis
124 significant production
125 strains
126 survival
127 transmission
128 tuberculosis
129 tuberculosis complex (MTBC) evolution
130 tuberculosis lineage 4 evade host defense
131 vesicles
132 virulence
133 schema:name Clinical isolates of the modern Mycobacterium tuberculosis lineage 4 evade host defense in human macrophages through eluding IL-1β-induced autophagy
134 schema:pagination 624
135 schema:productId N164dc3d077334045b40f8bbc1ead686d
136 N34a8ea87fb124642958b62df7c9080e5
137 Ndbb96a36b13c45d2b6dc51bdec2341f4
138 schema:sameAs https://app.dimensions.ai/details/publication/pub.1104158452
139 https://doi.org/10.1038/s41419-018-0640-8
140 schema:sdDatePublished 2022-01-01T18:47
141 schema:sdLicense https://scigraph.springernature.com/explorer/license/
142 schema:sdPublisher N020577bd52f8481fa6dd9f20702f9c74
143 schema:url https://doi.org/10.1038/s41419-018-0640-8
144 sgo:license sg:explorer/license/
145 sgo:sdDataset articles
146 rdf:type schema:ScholarlyArticle
147 N020577bd52f8481fa6dd9f20702f9c74 schema:name Springer Nature - SN SciGraph project
148 rdf:type schema:Organization
149 N164dc3d077334045b40f8bbc1ead686d schema:name doi
150 schema:value 10.1038/s41419-018-0640-8
151 rdf:type schema:PropertyValue
152 N17a644dbacf949fba07e0fc70c0cd731 rdf:first sg:person.01202453300.95
153 rdf:rest Nb9e874ea211d4313a49783bd2fd60e13
154 N1bd5c319c3264488885964fe45d05376 rdf:first sg:person.01130437467.18
155 rdf:rest Na3c7df4354454edd8c734c9618e69a9c
156 N27234a3ec0364e529bd360720c04fb25 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
157 schema:name Autophagy
158 rdf:type schema:DefinedTerm
159 N2a178db82d6b41d7a7ea260894c51690 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
160 schema:name Macrophages
161 rdf:type schema:DefinedTerm
162 N34a8ea87fb124642958b62df7c9080e5 schema:name dimensions_id
163 schema:value pub.1104158452
164 rdf:type schema:PropertyValue
165 N483af8a928b943468e70acd75f7f054e rdf:first sg:person.01200446072.99
166 rdf:rest Nddf6b5b2786c4261a7349270f41ce688
167 N59d8b0680685484c8121d56e27b110f7 rdf:first sg:person.01222655205.82
168 rdf:rest Na3a80203bbca469ab0f50e728c166e40
169 N69b1753e96744e609f46581e78d963a4 rdf:first sg:person.01026771172.24
170 rdf:rest Nfa6be8db34f4483db6768810eb7d44cc
171 N6ecceffc0c964ea48a5d93f6ade51bf7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
172 schema:name Interleukin-1beta
173 rdf:type schema:DefinedTerm
174 N70c250d71c9042188188b06e1945f857 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
175 schema:name Immune Evasion
176 rdf:type schema:DefinedTerm
177 N8761dddb99bd4b46880c16e7030f454f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
178 schema:name Phylogeny
179 rdf:type schema:DefinedTerm
180 N8a73eefbfe22469db5b49e9350a890a2 rdf:first sg:person.01064477442.53
181 rdf:rest N59d8b0680685484c8121d56e27b110f7
182 N8f3b281dd2e34a10ab3a9a734f725f9a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
183 schema:name Inflammation Mediators
184 rdf:type schema:DefinedTerm
185 N9e82a1e2951e4ed79f33cf3aa7fc2022 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
186 schema:name Host-Pathogen Interactions
187 rdf:type schema:DefinedTerm
188 Na3a80203bbca469ab0f50e728c166e40 rdf:first sg:person.01367573522.56
189 rdf:rest N483af8a928b943468e70acd75f7f054e
190 Na3c7df4354454edd8c734c9618e69a9c rdf:first sg:person.01316222666.31
191 rdf:rest Nec847dc8c7504b51830e93ef13a04397
192 Nab3704d9d8d0462aaef2e5deb477d130 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
193 schema:name Signal Transduction
194 rdf:type schema:DefinedTerm
195 Nb44ae07bafa749f8a5884e9db6b844e0 rdf:first sg:person.0755160366.91
196 rdf:rest N17a644dbacf949fba07e0fc70c0cd731
197 Nb4eb36bf92e54b0aadf5283c160c5eb6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
198 schema:name Autophagosomes
199 rdf:type schema:DefinedTerm
200 Nb9e874ea211d4313a49783bd2fd60e13 rdf:first sg:person.01006361171.07
201 rdf:rest N8a73eefbfe22469db5b49e9350a890a2
202 Nbb0b5dc5f7074afc89847e2a11b54035 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
203 schema:name Mycobacterium tuberculosis
204 rdf:type schema:DefinedTerm
205 Nc30525b60a2d444985070eb354c169a6 schema:volumeNumber 9
206 rdf:type schema:PublicationVolume
207 Nd56dac0d075a493dbc57dabfa106be24 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
208 schema:name Humans
209 rdf:type schema:DefinedTerm
210 Ndbb96a36b13c45d2b6dc51bdec2341f4 schema:name pubmed_id
211 schema:value 29795378
212 rdf:type schema:PropertyValue
213 Nddf6b5b2786c4261a7349270f41ce688 rdf:first sg:person.0741346170.03
214 rdf:rest rdf:nil
215 Neb1961664c554e2794c39c0f3d7e622a schema:issueNumber 6
216 rdf:type schema:PublicationIssue
217 Nec847dc8c7504b51830e93ef13a04397 rdf:first sg:person.01161317047.40
218 rdf:rest N69b1753e96744e609f46581e78d963a4
219 Nfa6be8db34f4483db6768810eb7d44cc rdf:first sg:person.01346531721.17
220 rdf:rest Nb44ae07bafa749f8a5884e9db6b844e0
221 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
222 schema:name Medical and Health Sciences
223 rdf:type schema:DefinedTerm
224 anzsrc-for:1107 schema:inDefinedTermSet anzsrc-for:
225 schema:name Immunology
226 rdf:type schema:DefinedTerm
227 sg:grant.6853760 http://pending.schema.org/fundedItem sg:pub.10.1038/s41419-018-0640-8
228 rdf:type schema:MonetaryGrant
229 sg:journal.1042939 schema:issn 2041-4889
230 schema:name Cell Death & Disease
231 schema:publisher Springer Nature
232 rdf:type schema:Periodical
233 sg:person.01006361171.07 schema:affiliation grid-institutes:grid.411075.6
234 schema:familyName Sali
235 schema:givenName Michela
236 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01006361171.07
237 rdf:type schema:Person
238 sg:person.01026771172.24 schema:affiliation grid-institutes:grid.411075.6
239 schema:familyName Camassa
240 schema:givenName Serena
241 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01026771172.24
242 rdf:type schema:Person
243 sg:person.01064477442.53 schema:affiliation grid-institutes:grid.9906.6
244 schema:familyName Dini
245 schema:givenName Luciana
246 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01064477442.53
247 rdf:type schema:Person
248 sg:person.01130437467.18 schema:affiliation grid-institutes:grid.414603.4
249 schema:familyName Romagnoli
250 schema:givenName Alessandra
251 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01130437467.18
252 rdf:type schema:Person
253 sg:person.01161317047.40 schema:affiliation grid-institutes:grid.411075.6
254 schema:familyName Palucci
255 schema:givenName Ivana
256 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01161317047.40
257 rdf:type schema:Person
258 sg:person.01200446072.99 schema:affiliation grid-institutes:grid.414603.4
259 schema:familyName Goletti
260 schema:givenName Delia
261 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01200446072.99
262 rdf:type schema:Person
263 sg:person.01202453300.95 schema:affiliation grid-institutes:grid.9906.6
264 schema:familyName Mariano
265 schema:givenName Stefania
266 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01202453300.95
267 rdf:type schema:Person
268 sg:person.01222655205.82 schema:affiliation grid-institutes:grid.414603.4
269 schema:familyName Girardi
270 schema:givenName Enrico
271 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01222655205.82
272 rdf:type schema:Person
273 sg:person.01316222666.31 schema:affiliation grid-institutes:grid.414603.4
274 schema:familyName Petruccioli
275 schema:givenName Elisa
276 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01316222666.31
277 rdf:type schema:Person
278 sg:person.01346531721.17 schema:affiliation grid-institutes:grid.9906.6
279 schema:familyName Carata
280 schema:givenName Elisabetta
281 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01346531721.17
282 rdf:type schema:Person
283 sg:person.01367573522.56 schema:affiliation grid-institutes:grid.411075.6
284 schema:familyName Delogu
285 schema:givenName Giovanni
286 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01367573522.56
287 rdf:type schema:Person
288 sg:person.0741346170.03 schema:affiliation grid-institutes:grid.9906.6
289 schema:familyName Fimia
290 schema:givenName Gian Maria
291 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0741346170.03
292 rdf:type schema:Person
293 sg:person.0755160366.91 schema:affiliation grid-institutes:grid.414603.4
294 schema:familyName Petrone
295 schema:givenName Linda
296 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0755160366.91
297 rdf:type schema:Person
298 sg:pub.10.1007/82_2013_332 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020601145
299 https://doi.org/10.1007/82_2013_332
300 rdf:type schema:CreativeWork
301 sg:pub.10.1007/s10875-014-0103-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025325690
302 https://doi.org/10.1007/s10875-014-0103-7
303 rdf:type schema:CreativeWork
304 sg:pub.10.1038/mi.2011.14 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013828195
305 https://doi.org/10.1038/mi.2011.14
306 rdf:type schema:CreativeWork
307 sg:pub.10.1038/nature02837 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017834156
308 https://doi.org/10.1038/nature02837
309 rdf:type schema:CreativeWork
310 sg:pub.10.1038/nature16451 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033165191
311 https://doi.org/10.1038/nature16451
312 rdf:type schema:CreativeWork
313 sg:pub.10.1038/ncomms11290 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010683868
314 https://doi.org/10.1038/ncomms11290
315 rdf:type schema:CreativeWork
316 sg:pub.10.1038/ni.3273 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025859742
317 https://doi.org/10.1038/ni.3273
318 rdf:type schema:CreativeWork
319 sg:pub.10.1038/nrd.2017.162 schema:sameAs https://app.dimensions.ai/details/publication/pub.1091891119
320 https://doi.org/10.1038/nrd.2017.162
321 rdf:type schema:CreativeWork
322 sg:pub.10.1038/nrd4696 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002419266
323 https://doi.org/10.1038/nrd4696
324 rdf:type schema:CreativeWork
325 sg:pub.10.1038/nri3532 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022777012
326 https://doi.org/10.1038/nri3532
327 rdf:type schema:CreativeWork
328 sg:pub.10.1038/nrmicro.2018.8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1101104614
329 https://doi.org/10.1038/nrmicro.2018.8
330 rdf:type schema:CreativeWork
331 sg:pub.10.1038/srep16320 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004656238
332 https://doi.org/10.1038/srep16320
333 rdf:type schema:CreativeWork
334 sg:pub.10.1038/srep23089 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043291608
335 https://doi.org/10.1038/srep23089
336 rdf:type schema:CreativeWork
337 grid-institutes:grid.411075.6 schema:alternateName Institute of Microbiology, Universita’ Cattolica del Sacro Cuore – Fondazione Policlinico Gemelli, Rome, 00168 Italy
338 schema:name Institute of Microbiology, Universita’ Cattolica del Sacro Cuore – Fondazione Policlinico Gemelli, Rome, 00168 Italy
339 rdf:type schema:Organization
340 grid-institutes:grid.414603.4 schema:alternateName Department of Epidemiology and Preclinical Research, National Institutes for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, 00149 Italy
341 schema:name Department of Epidemiology and Preclinical Research, National Institutes for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, 00149 Italy
342 rdf:type schema:Organization
343 grid-institutes:grid.9906.6 schema:alternateName Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, University of Salento, Lecce, 73100 Italy
344 schema:name Department of Epidemiology and Preclinical Research, National Institutes for Infectious Diseases Lazzaro Spallanzani IRCCS, Rome, 00149 Italy
345 Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, University of Salento, Lecce, 73100 Italy
346 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...