TOLLIP deficiency is associated with increased resistance to Legionella pneumophila pneumonia
Identifieur interne : 000403 ( Main/Exploration ); précédent : 000402; suivant : 000404TOLLIP deficiency is associated with increased resistance to Legionella pneumophila pneumonia
Auteurs : Javeed A. Shah ; Robyn Emery ; Brian Lee ; Sambasivan Venkatasubramanian ; Jason D. Simmons ; Melanie Brown ; Chi F. Hung ; Jan M. Prins [Pays-Bas] ; Annelies Verbon [Pays-Bas] ; Thomas R. Hawn ; Shawn J. SkerrettSource :
- Mucosal immunology [ 1933-0219 ] ; 2019.
Abstract
Url:
DOI: 10.1038/s41385-019-0196-7
PubMed: 31462698
PubMed Central: 6824992
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">TOLLIP deficiency is associated with increased resistance to <italic>Legionella pneumophila</italic> pneumonia</title><author><name sortKey="Shah, Javeed A" sort="Shah, Javeed A" uniqKey="Shah J" first="Javeed A." last="Shah">Javeed A. Shah</name><affiliation><nlm:aff id="A1">Department of Medicine, University of Washington School of Medicine, Seattle, Washington.</nlm:aff><wicri:noCountry code="subfield">Washington.</wicri:noCountry></affiliation><affiliation><nlm:aff id="A2">Veterans Affairs Puget Sound Health Care System, Seattle, Washington.</nlm:aff><wicri:noCountry code="subfield">Washington.</wicri:noCountry></affiliation></author><author><name sortKey="Emery, Robyn" sort="Emery, Robyn" uniqKey="Emery R" first="Robyn" last="Emery">Robyn Emery</name><affiliation><nlm:aff id="A1">Department of Medicine, University of Washington School of Medicine, Seattle, Washington.</nlm:aff><wicri:noCountry code="subfield">Washington.</wicri:noCountry></affiliation></author><author><name sortKey="Lee, Brian" sort="Lee, Brian" uniqKey="Lee B" first="Brian" last="Lee">Brian Lee</name><affiliation><nlm:aff id="A1">Department of Medicine, University of Washington School of Medicine, Seattle, Washington.</nlm:aff><wicri:noCountry code="subfield">Washington.</wicri:noCountry></affiliation></author><author><name sortKey="Venkatasubramanian, Sambasivan" sort="Venkatasubramanian, Sambasivan" uniqKey="Venkatasubramanian S" first="Sambasivan" last="Venkatasubramanian">Sambasivan Venkatasubramanian</name><affiliation><nlm:aff id="A1">Department of Medicine, University of Washington School of Medicine, Seattle, Washington.</nlm:aff><wicri:noCountry code="subfield">Washington.</wicri:noCountry></affiliation></author><author><name sortKey="Simmons, Jason D" sort="Simmons, Jason D" uniqKey="Simmons J" first="Jason D." last="Simmons">Jason D. Simmons</name><affiliation><nlm:aff id="A1">Department of Medicine, University of Washington School of Medicine, Seattle, Washington.</nlm:aff><wicri:noCountry code="subfield">Washington.</wicri:noCountry></affiliation></author><author><name sortKey="Brown, Melanie" sort="Brown, Melanie" uniqKey="Brown M" first="Melanie" last="Brown">Melanie Brown</name><affiliation><nlm:aff id="A1">Department of Medicine, University of Washington School of Medicine, Seattle, Washington.</nlm:aff><wicri:noCountry code="subfield">Washington.</wicri:noCountry></affiliation></author><author><name sortKey="Hung, Chi F" sort="Hung, Chi F" uniqKey="Hung C" first="Chi F." last="Hung">Chi F. Hung</name><affiliation><nlm:aff id="A1">Department of Medicine, University of Washington School of Medicine, Seattle, Washington.</nlm:aff><wicri:noCountry code="subfield">Washington.</wicri:noCountry></affiliation></author><author><name sortKey="Prins, Jan M" sort="Prins, Jan M" uniqKey="Prins J" first="Jan M." last="Prins">Jan M. Prins</name><affiliation wicri:level="4"><nlm:aff id="A4">University of Amsterdam, Amsterdam, the Netherlands.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>University of Amsterdam, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName><orgName type="university">Université d'Amsterdam</orgName></affiliation></author><author><name sortKey="Verbon, Annelies" sort="Verbon, Annelies" uniqKey="Verbon A" first="Annelies" last="Verbon">Annelies Verbon</name><affiliation wicri:level="3"><nlm:aff id="A3">Erasmus Medical Center, Rotterdam, the Netherlands.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Erasmus Medical Center, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Hawn, Thomas R" sort="Hawn, Thomas R" uniqKey="Hawn T" first="Thomas R." last="Hawn">Thomas R. Hawn</name><affiliation><nlm:aff id="A1">Department of Medicine, University of Washington School of Medicine, Seattle, Washington.</nlm:aff><wicri:noCountry code="subfield">Washington.</wicri:noCountry></affiliation></author><author><name sortKey="Skerrett, Shawn J" sort="Skerrett, Shawn J" uniqKey="Skerrett S" first="Shawn J." last="Skerrett">Shawn J. Skerrett</name><affiliation><nlm:aff id="A1">Department of Medicine, University of Washington School of Medicine, Seattle, Washington.</nlm:aff><wicri:noCountry code="subfield">Washington.</wicri:noCountry></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31462698</idno><idno type="pmc">6824992</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824992</idno><idno type="RBID">PMC:6824992</idno><idno type="doi">10.1038/s41385-019-0196-7</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000853</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000853</idno><idno type="wicri:Area/Pmc/Curation">000853</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000853</idno><idno type="wicri:Area/Pmc/Checkpoint">000364</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000364</idno><idno type="wicri:Area/Ncbi/Merge">000976</idno><idno type="wicri:Area/Ncbi/Curation">000976</idno><idno type="wicri:Area/Ncbi/Checkpoint">000976</idno><idno type="wicri:doubleKey">1933-0219:2019:Shah J:tollip:deficiency:is</idno><idno type="wicri:Area/Main/Merge">000403</idno><idno type="wicri:Area/Main/Curation">000403</idno><idno type="wicri:Area/Main/Exploration">000403</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">TOLLIP deficiency is associated with increased resistance to <italic>Legionella pneumophila</italic> pneumonia</title><author><name sortKey="Shah, Javeed A" sort="Shah, Javeed A" uniqKey="Shah J" first="Javeed A." last="Shah">Javeed A. Shah</name><affiliation><nlm:aff id="A1">Department of Medicine, University of Washington School of Medicine, Seattle, Washington.</nlm:aff><wicri:noCountry code="subfield">Washington.</wicri:noCountry></affiliation><affiliation><nlm:aff id="A2">Veterans Affairs Puget Sound Health Care System, Seattle, Washington.</nlm:aff><wicri:noCountry code="subfield">Washington.</wicri:noCountry></affiliation></author><author><name sortKey="Emery, Robyn" sort="Emery, Robyn" uniqKey="Emery R" first="Robyn" last="Emery">Robyn Emery</name><affiliation><nlm:aff id="A1">Department of Medicine, University of Washington School of Medicine, Seattle, Washington.</nlm:aff><wicri:noCountry code="subfield">Washington.</wicri:noCountry></affiliation></author><author><name sortKey="Lee, Brian" sort="Lee, Brian" uniqKey="Lee B" first="Brian" last="Lee">Brian Lee</name><affiliation><nlm:aff id="A1">Department of Medicine, University of Washington School of Medicine, Seattle, Washington.</nlm:aff><wicri:noCountry code="subfield">Washington.</wicri:noCountry></affiliation></author><author><name sortKey="Venkatasubramanian, Sambasivan" sort="Venkatasubramanian, Sambasivan" uniqKey="Venkatasubramanian S" first="Sambasivan" last="Venkatasubramanian">Sambasivan Venkatasubramanian</name><affiliation><nlm:aff id="A1">Department of Medicine, University of Washington School of Medicine, Seattle, Washington.</nlm:aff><wicri:noCountry code="subfield">Washington.</wicri:noCountry></affiliation></author><author><name sortKey="Simmons, Jason D" sort="Simmons, Jason D" uniqKey="Simmons J" first="Jason D." last="Simmons">Jason D. Simmons</name><affiliation><nlm:aff id="A1">Department of Medicine, University of Washington School of Medicine, Seattle, Washington.</nlm:aff><wicri:noCountry code="subfield">Washington.</wicri:noCountry></affiliation></author><author><name sortKey="Brown, Melanie" sort="Brown, Melanie" uniqKey="Brown M" first="Melanie" last="Brown">Melanie Brown</name><affiliation><nlm:aff id="A1">Department of Medicine, University of Washington School of Medicine, Seattle, Washington.</nlm:aff><wicri:noCountry code="subfield">Washington.</wicri:noCountry></affiliation></author><author><name sortKey="Hung, Chi F" sort="Hung, Chi F" uniqKey="Hung C" first="Chi F." last="Hung">Chi F. Hung</name><affiliation><nlm:aff id="A1">Department of Medicine, University of Washington School of Medicine, Seattle, Washington.</nlm:aff><wicri:noCountry code="subfield">Washington.</wicri:noCountry></affiliation></author><author><name sortKey="Prins, Jan M" sort="Prins, Jan M" uniqKey="Prins J" first="Jan M." last="Prins">Jan M. Prins</name><affiliation wicri:level="4"><nlm:aff id="A4">University of Amsterdam, Amsterdam, the Netherlands.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>University of Amsterdam, Amsterdam</wicri:regionArea><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName><orgName type="university">Université d'Amsterdam</orgName></affiliation></author><author><name sortKey="Verbon, Annelies" sort="Verbon, Annelies" uniqKey="Verbon A" first="Annelies" last="Verbon">Annelies Verbon</name><affiliation wicri:level="3"><nlm:aff id="A3">Erasmus Medical Center, Rotterdam, the Netherlands.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Pays-Bas</country><wicri:regionArea>Erasmus Medical Center, Rotterdam</wicri:regionArea><placeName><settlement type="city">Rotterdam</settlement><region nuts="2" type="province">Hollande-Méridionale</region></placeName></affiliation></author><author><name sortKey="Hawn, Thomas R" sort="Hawn, Thomas R" uniqKey="Hawn T" first="Thomas R." last="Hawn">Thomas R. Hawn</name><affiliation><nlm:aff id="A1">Department of Medicine, University of Washington School of Medicine, Seattle, Washington.</nlm:aff><wicri:noCountry code="subfield">Washington.</wicri:noCountry></affiliation></author><author><name sortKey="Skerrett, Shawn J" sort="Skerrett, Shawn J" uniqKey="Skerrett S" first="Shawn J." last="Skerrett">Shawn J. Skerrett</name><affiliation><nlm:aff id="A1">Department of Medicine, University of Washington School of Medicine, Seattle, Washington.</nlm:aff><wicri:noCountry code="subfield">Washington.</wicri:noCountry></affiliation></author></analytic><series><title level="j">Mucosal immunology</title><idno type="ISSN">1933-0219</idno><idno type="eISSN">1935-3456</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P2"><italic>Legionella pneumophila</italic> (Lp) is a flagellated, intracellular bacterium that can cause Legionnaires’ disease (LD). Lp activates multiple innate immune receptors, and TOLLIP dampens MyD88-dependent signaling and may influence susceptibility to LD. We evaluated the effect of TOLLIP on innate immunity, pneumonia severity, and LD susceptibility in mouse lungs and human populations. To accomplish this, we evaluated the effect of TOLLIP on lung-specific Lp control and immune response and associated a common functional TOLLIP variant with Lp-induced innate immune responses and LD susceptibility in humans. After aerosol Lp infection, <italic>Tollip</italic><sup>−/−</sup> mice demonstrated significantly fewer bacterial CFU and increased cytokine responses from BAL fluid. <italic>Tollip</italic><sup>−/−</sup> macrophages also suppressed intracellular Lp replication in a flagellin-independent manner. The presence of a previously characterized, functionally active SNP associated with decreased TOLLIP mRNA transcript in monocytes was associated with increased TNF and IL-6 secretion after Lp stimulation of PBMC <italic>ex vivo.</italic> This genotype was separately associated with decreased LD susceptibility (309 controls, 88 cases, p = 0.008, OR 0.36, 95% CI 0.16 – 0.76) in a candidate gene association study. These results suggest that TOLLIP decreases lung-specific TLR responses to increase LD susceptibility in human populations. Better understanding of TOLLIP may lead to novel immunomodulatory therapies.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Phin, N" uniqKey="Phin N">N Phin</name></author><author><name sortKey="Parry Ford, F" uniqKey="Parry Ford F">F Parry-Ford</name></author><author><name sortKey="Harrison, T" uniqKey="Harrison T">T Harrison</name></author><author><name sortKey="Stagg, Hr" uniqKey="Stagg H">HR Stagg</name></author><author><name sortKey="Zhang, N" uniqKey="Zhang N">N Zhang</name></author><author><name sortKey="Kumar, K" uniqKey="Kumar K">K Kumar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Dominguez, A" uniqKey="Dominguez A">A Dominguez</name></author><author><name sortKey="Alvarez, J" uniqKey="Alvarez J">J Alvarez</name></author><author><name sortKey="Sabria, M" uniqKey="Sabria M">M Sabria</name></author><author><name sortKey="Carmona, G" uniqKey="Carmona G">G 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sort="Hawn, Thomas R" uniqKey="Hawn T" first="Thomas R." last="Hawn">Thomas R. Hawn</name><name sortKey="Hung, Chi F" sort="Hung, Chi F" uniqKey="Hung C" first="Chi F." last="Hung">Chi F. Hung</name><name sortKey="Lee, Brian" sort="Lee, Brian" uniqKey="Lee B" first="Brian" last="Lee">Brian Lee</name><name sortKey="Shah, Javeed A" sort="Shah, Javeed A" uniqKey="Shah J" first="Javeed A." last="Shah">Javeed A. Shah</name><name sortKey="Simmons, Jason D" sort="Simmons, Jason D" uniqKey="Simmons J" first="Jason D." last="Simmons">Jason D. Simmons</name><name sortKey="Skerrett, Shawn J" sort="Skerrett, Shawn J" uniqKey="Skerrett S" first="Shawn J." last="Skerrett">Shawn J. Skerrett</name><name sortKey="Venkatasubramanian, Sambasivan" sort="Venkatasubramanian, Sambasivan" uniqKey="Venkatasubramanian S" first="Sambasivan" last="Venkatasubramanian">Sambasivan Venkatasubramanian</name></noCountry><country name="Pays-Bas"><region name="Hollande-Septentrionale"><name sortKey="Prins, Jan M" sort="Prins, Jan M" uniqKey="Prins J" first="Jan M." last="Prins">Jan M. Prins</name></region><name sortKey="Verbon, Annelies" sort="Verbon, Annelies" uniqKey="Verbon A" first="Annelies" last="Verbon">Annelies Verbon</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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