{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:36:14Z","timestamp":1792521374199,"version":"4.5.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T00:00:00Z","timestamp":1656547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012456","name":"National Social Science Fund of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012456","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Pulmonary epithelial barrier dysfunction is a critical pathophysiological process in pneumonia and associated invasive infections, such as those caused by\n                    <jats:italic>Acinetobacter baumannii<\/jats:italic>\n                    . However, the mechanisms underlying\n                    <jats:italic>A. baumannii<\/jats:italic>\n                    -induced pulmonary epithelial barrier dysfunction and bacterial translocation remain unclear. In this study, lungs of mice and A549 human epithelial cell monolayers were challenged with the\n                    <jats:italic>A. baumannii<\/jats:italic>\n                    wild-type strain and an outer membrane protein A (\n                    <jats:italic>ompA<\/jats:italic>\n                    ) deletion strain. In addition, epithelial cells in culture were treated with purified OmpA protein or transfected with a eukaryotic expression vector encoding\n                    <jats:italic>ompA<\/jats:italic>\n                    (pCMV-\n                    <jats:italic>ompA<\/jats:italic>\n                    ). Bacterial translocation across cell monolayers and intrapulmonary burden were measured, barrier function was evaluated\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    ; cell migration ability was determined. The specific inhibitors C29 and JSH-23 were used to suppress the activity of Toll-like receptor 2 (TLR2) and of NF-\u03baB, respectively. IQ-GTPase-activating protein 1 (IQGAP1) small interfering RNA was used to knock down endogenous IQGAP1 expression. In this work, we show that OmpA from\n                    <jats:italic>A. baumannii<\/jats:italic>\n                    increased the production of pro-inflammatory cytokines, remodeled the cytoskeleton, and internalized intercellular adherens junctions (AJs); these changes eventually induced pulmonary epithelial barrier dysfunction to promote bacterial translocation. IQGAP1-targeting small interfering RNA and chemical inhibition of TLR2 or NF-\u03baB prevented high permeability of the pulmonary epithelial barrier. TLR2\/NF-\u03baB signaling was involved in OmpA-induced inflammation, IQGAP1-mediated OmpA-induced opening of the pulmonary epithelial barrier\n                    <jats:italic>via<\/jats:italic>\n                    cytoskeleton dynamic remodeling, and cellular redistribution of the major AJ protein, E-cadherin. These observations indicate that\n                    <jats:italic>A. baumannii<\/jats:italic>\n                    uses OmpA to overcome epithelial defences and cross the pulmonary epithelial barrier.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2022.927955","type":"journal-article","created":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T03:45:51Z","timestamp":1656560751000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":29,"title":["Acinetobacter baumannii Outer Membrane Protein A Induces Pulmonary Epithelial Barrier Dysfunction and Bacterial Translocation Through The TLR2\/IQGAP1 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