{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T02:01:13Z","timestamp":1793152873141,"version":"4.5.0"},"reference-count":48,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T00:00:00Z","timestamp":1671062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020 Fast Track to Innovation Pilot-2015-1 Program","award":["720480\u2014ID-LYME"],"award-info":[{"award-number":["720480\u2014ID-LYME"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Chlamydia trachomatis (Ct) is the most common cause of genital tract infections as well as preventable blindness worldwide. Pattern recognition receptors such as toll-like receptors (TLRs) represent the initial step in recognizing pathogenic microorganisms and are crucial for the initiation of an appropriate immune response. However, our understanding of TLR-signaling in Chlamydia-infected immune cells is incomplete. For a better comprehension of pathological inflammatory responses, robust models for interrogating TLR-signaling upon chlamydial infections are needed. To analyze the TLR response, we developed and utilized a highly sensitive and selective fluorescent transcriptional cellular reporter system to measure the activity of the transcription factor NF-\u03baB. Upon incubation of the reporter cells with different preparations of Ct, we were able to pinpoint which components of TLRs are involved in the recognition of Ct. We identified CD14 associated with unique characteristics of different serovars as the crucial factor of the TLR4\/CD14\/MD2 complex for Ct-mediated activation of the NF-\u03baB pathway. Furthermore, we found the TLR4\/CD14\/MD2 complex to be decisive for the uptake of Ct-derived lipopolysaccharides but not for infection and replication of Ct. Imaging flow cytometry provided information about inclusion formation in myeloid- as well as lymphocytic cells and was highest for Ct L2 with at least 25% of inclusion forming cells. Ct E inclusion formation was eminent in Jurkat cells without CD14 expression (11.1%). Thus, our model enables to determine Ct uptake and signal induction by pinpointing individual components of the recognition and signaling pathways to better understand the immune response towards infectious pathogens.<\/jats:p>","DOI":"10.3390\/microorganisms10122489","type":"journal-article","created":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T02:16:41Z","timestamp":1671157001000},"page":"2489","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["TLR4\/CD14\/MD2 Revealed as the Limited Toll-like Receptor Complex for Chlamydia trachomatis-Induced NF-\u03baB Signaling"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2689-5159","authenticated-orcid":false,"given":"Romana","family":"Klasinc","sequence":"first","affiliation":[{"name":"Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Battin","sequence":"additional","affiliation":[{"name":"Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Division of Immune Receptors and T Cell Activation, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Paster","sequence":"additional","affiliation":[{"name":"Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Division of Immune Receptors and T Cell Activation, 1090 Vienna, Austria"},{"name":"St. Anna Children\u2019s Cancer Research Institute (CCRI), 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7435-7999","authenticated-orcid":false,"given":"Michael","family":"Reiter","sequence":"additional","affiliation":[{"name":"Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Schatzlmaier","sequence":"additional","affiliation":[{"name":"Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Rhein","sequence":"additional","affiliation":[{"name":"Luminex B.V., A DiaSorin Company, 5215 MV \u2018s-Hertogenbosch, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2657-6836","authenticated-orcid":false,"given":"Andreas","family":"Spittler","sequence":"additional","affiliation":[{"name":"Medical University of Vienna, Core Facility Flow Cytometry and Department of Surgery, Research Laboratories, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6848-4097","authenticated-orcid":false,"given":"Peter","family":"Steinberger","sequence":"additional","affiliation":[{"name":"Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute of Immunology, Division of Immune Receptors and T Cell Activation, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6404-4430","authenticated-orcid":false,"given":"Hannes","family":"Stockinger","sequence":"additional","affiliation":[{"name":"Medical University of Vienna, Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e235","DOI":"10.1016\/S1473-3099(17)30310-9","article-title":"Sexually transmitted infections: Challenges ahead","volume":"17","author":"Unemo","year":"2017","journal-title":"Lancet. 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