1
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: not found
      • Article: not found

      Chlamydia pneumoniae Hijacks a Host Autoregulatory IL-1β Loop to Drive Foam Cell Formation and Accelerate Atherosclerosis

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          <p id="P3">Pathogen burden accelerate atherosclerosis, but the mechanisms remain unresolved. Activation of the NLRP3 inflammasome is linked to atherogenesis. Here we investigated whether <i>Chlamydia pneumoniae</i> ( <i>C.pn)</i> infection engages NLRP3 in promoting atherosclerosis. <i>C.pn</i> potentiated hyperlipidemia-induced inflammasome activity in cultured macrophages and in foam cells in atherosclerotic lesions of <i>Ldlr <sup>−/−</sup> </i> mice. <i>C.pn</i>-induced acceleration of atherosclerosis was significantly dependent on NLRP3 and Caspase-1. We discovered that <i>C.pn</i>-induced extracellular IL-1β triggers a negative feedback loop to inhibit GPR109a and ABCA1 expression and cholesterol efflux leading to accumulation of intracellular cholesterol and foam cell formation. <i>Gpr109a</i> and <i>Abca1</i> were both upregulated in plaque lesions in <i>Nlrp3 <sup>−/−</sup> </i> mice in both hyperlipidemic and <i>C.pn</i> infection models. Mature IL-1β and cholesterol may compete for access to the ABCA1 transporter to be exported from macrophages. <i>C.pn</i> exploits this metabolic-immune cross talk, which can be modulated by NLRP3 inhibitors to alleviate atherosclerosis. </p><p id="P4">Infections can accelerate atherosclerosis, but the mechanisms remain unresolved. Tumurkhuu et al. show that <i>C.pn</i> infection-induced IL-1β institutes negative feedback to inhibit Gpr109a, ABCA1 expression, and cholesterol efflux leading to accumulation of intracellular cholesterol. Mature IL-1β can use ABCA1 for secretion from macrophages at the detriment of cholesterol efflux. </p><p id="P5"> <div class="figure-container so-text-align-c"> <img alt="" class="figure" src="/document_file/2ad5702b-a206-47fe-a608-6f1971a0f581/PubMedCentral/image/nihms976312u1.jpg"/> </div> </p>

          Related collections

          Author and article information

          Journal
          Cell Metabolism
          Cell Metabolism
          Elsevier BV
          15504131
          September 2018
          September 2018
          : 28
          : 3
          : 432-448.e4
          Article
          10.1016/j.cmet.2018.05.027
          6125162
          29937375
          b3ebab07-c72b-4160-b0ae-136e87b88608
          © 2018

          https://www.elsevier.com/tdm/userlicense/1.0/

          History

          Comments

          Comment on this article