Porphyromonas gingivalis attenuates ATP-mediated inflammasome activation and HMGB1 release through expression of a nucleoside-diphosphate kinase
Identifieur interne : 002627 ( Pmc/Curation ); précédent : 002626; suivant : 002628Porphyromonas gingivalis attenuates ATP-mediated inflammasome activation and HMGB1 release through expression of a nucleoside-diphosphate kinase
Auteurs : Larry Johnson [États-Unis] ; Kalina R. Atanasova [États-Unis] ; Phuong Q. Bui [États-Unis] ; Jungnam Lee [États-Unis] ; Shu-Chen Hung [États-Unis] ; Özlem Yilmaz [États-Unis] ; David M. Ojcius [États-Unis]Source :
- Microbes and infection / Institut Pasteur [ 1286-4579 ] ; 2015.
Abstract
Many intracellular pathogens evade the innate immune response in order to survive and proliferate within infected cells. We show that
Url:
DOI: 10.1016/j.micinf.2015.03.010
PubMed: 25828169
PubMed Central: 4426005
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<front><div type="abstract" xml:lang="en"><p id="P1">Many intracellular pathogens evade the innate immune response in order to survive and proliferate within infected cells. We show that <italic>Porphyromonas gingivalis</italic>
, an intracellular opportunistic pathogen, uses a nucleoside-diphosphate kinase (NDK) homolog to inhibit innate immune responses due to stimulation by extracellular ATP, which acts as a danger signal that binds to P2X<sub>7</sub>
receptors and induces activation of an inflammasome and caspase-1. Thus, infection of gingival epithelial cells (GECs) with wild-type <italic>P. gingivalis</italic>
results in inhibition of ATP-induced caspase-1 activation. However, <italic>ndk</italic>
-deficient <italic>P. gingivalis</italic>
is less effective than wild-type <italic>P. gingivalis</italic>
in reducing ATP-mediated caspase-1 activation and secretion of the proinflammatory cytokine, IL-1β, from infected GECs. Furthermore, <italic>P. gingivalis</italic>
NDK modulates release of high-mobility group protein B1 (HMGB1), a pro-inflammatory danger signal, which remains associated with chromatin in healthy cells. Unexpectedly, infection with either wild-type or <italic>ndk</italic>
-deficient <italic>P. gingivalis</italic>
causes release of HMGB1 from the nucleus to the cytosol. But HMGB1 is released to the extracellular space when uninfected GECs are further stimulated with ATP, and there is more HMGB1 released from the cells when ATP-treated cells are infected with <italic>ndk</italic>
-deficient mutant than wild-type <italic>P. gingivalis</italic>
. Our results reveal that NDK plays a significant role in inhibiting P2X<sub>7</sub>
-dependent inflammasome activation and HMGB1 release from infected GECs.</p>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">100883508</journal-id>
<journal-id journal-id-type="pubmed-jr-id">21592</journal-id>
<journal-id journal-id-type="nlm-ta">Microbes Infect</journal-id>
<journal-id journal-id-type="iso-abbrev">Microbes Infect.</journal-id>
<journal-title-group><journal-title>Microbes and infection / Institut Pasteur</journal-title>
</journal-title-group>
<issn pub-type="ppub">1286-4579</issn>
<issn pub-type="epub">1769-714X</issn>
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<article-meta><article-id pub-id-type="pmid">25828169</article-id>
<article-id pub-id-type="pmc">4426005</article-id>
<article-id pub-id-type="doi">10.1016/j.micinf.2015.03.010</article-id>
<article-id pub-id-type="manuscript">NIHMS673985</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title><italic>Porphyromonas gingivalis</italic>
attenuates ATP-mediated inflammasome activation and HMGB1 release through expression of a nucleoside-diphosphate kinase</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Johnson</surname>
<given-names>Larry</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
<xref ref-type="aff" rid="A2">b</xref>
<xref rid="FN2" ref-type="author-notes">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Atanasova</surname>
<given-names>Kalina R.</given-names>
</name>
<xref ref-type="aff" rid="A3">c</xref>
<xref ref-type="aff" rid="A4">d</xref>
<xref rid="FN2" ref-type="author-notes">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bui</surname>
<given-names>Phuong Q.</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
<xref ref-type="aff" rid="A2">b</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lee</surname>
<given-names>Jungnam</given-names>
</name>
<xref ref-type="aff" rid="A3">c</xref>
<xref ref-type="aff" rid="A4">d</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hung</surname>
<given-names>Shu-Chen</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
<xref ref-type="aff" rid="A2">b</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Yilmaz</surname>
<given-names>Özlem</given-names>
</name>
<xref ref-type="aff" rid="A3">c</xref>
<xref ref-type="aff" rid="A4">d</xref>
<xref rid="FN1" ref-type="author-notes">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ojcius</surname>
<given-names>David M.</given-names>
</name>
<xref ref-type="aff" rid="A1">a</xref>
<xref ref-type="aff" rid="A2">b</xref>
<xref rid="FN1" ref-type="author-notes">*</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>a</label>
Department of Molecular Cell Biology, University of California, Merced, CA 95343, USA</aff>
<aff id="A2"><label>b</label>
Health Sciences Research Institute, University of California, Merced, CA 95343, USA</aff>
<aff id="A3"><label>c</label>
Department of Periodontology, University of Florida, Gainesville, FL 32610, USA</aff>
<aff id="A4"><label>d</label>
Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610, USA</aff>
<author-notes><corresp id="FN1"><label>*</label>
Corresponding authors: Department of Molecular Cell Biology, University of California, 5200 North Lake Road, Merced, CA 95343, USA. Tele: +1 209 228 2948, <email>david.ojcius@gmail.com</email>
, Or: Department of Periodontology, University of Florida, Gainesville, FL 32610, USA. Tele: +1 352 273 8003, <email>oyilmaz@ufl.edu</email>
</corresp>
<fn id="FN2" fn-type="equal"><label>1</label>
<p>Both authors contributed equally to this work</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>23</day>
<month>3</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="epub"><day>27</day>
<month>3</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="ppub"><month>5</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>01</day>
<month>5</month>
<year>2016</year>
</pub-date>
<volume>17</volume>
<issue>5</issue>
<fpage>369</fpage>
<lpage>377</lpage>
<pmc-comment>elocation-id from pubmed: 10.1016/j.micinf.2015.03.010</pmc-comment>
<abstract><p id="P1">Many intracellular pathogens evade the innate immune response in order to survive and proliferate within infected cells. We show that <italic>Porphyromonas gingivalis</italic>
, an intracellular opportunistic pathogen, uses a nucleoside-diphosphate kinase (NDK) homolog to inhibit innate immune responses due to stimulation by extracellular ATP, which acts as a danger signal that binds to P2X<sub>7</sub>
receptors and induces activation of an inflammasome and caspase-1. Thus, infection of gingival epithelial cells (GECs) with wild-type <italic>P. gingivalis</italic>
results in inhibition of ATP-induced caspase-1 activation. However, <italic>ndk</italic>
-deficient <italic>P. gingivalis</italic>
is less effective than wild-type <italic>P. gingivalis</italic>
in reducing ATP-mediated caspase-1 activation and secretion of the proinflammatory cytokine, IL-1β, from infected GECs. Furthermore, <italic>P. gingivalis</italic>
NDK modulates release of high-mobility group protein B1 (HMGB1), a pro-inflammatory danger signal, which remains associated with chromatin in healthy cells. Unexpectedly, infection with either wild-type or <italic>ndk</italic>
-deficient <italic>P. gingivalis</italic>
causes release of HMGB1 from the nucleus to the cytosol. But HMGB1 is released to the extracellular space when uninfected GECs are further stimulated with ATP, and there is more HMGB1 released from the cells when ATP-treated cells are infected with <italic>ndk</italic>
-deficient mutant than wild-type <italic>P. gingivalis</italic>
. Our results reveal that NDK plays a significant role in inhibiting P2X<sub>7</sub>
-dependent inflammasome activation and HMGB1 release from infected GECs.</p>
</abstract>
<kwd-group><kwd>innate immunity</kwd>
<kwd>purinergic receptor</kwd>
<kwd><italic>Porphyromonas gingivalis</italic>
</kwd>
<kwd>interleukins</kwd>
<kwd>inflammation</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>
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