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PG is a microbe-associated molecular pattern, and two of its major pattern recognition receptors in human cells are nucleotide-binding oligomerization domain-containing proteins 1 and 2 (NOD1 and NOD2, respectively). It has been proposed that this unique morphological feature is evidence of pathoadaptation by the microbe, permitting PG-dependent cell division while also reducing the bacterium\u2019s recognition by innate immune receptors.\n                      <jats:italic toggle=\"yes\">Chlamydia trachomatis<\/jats:italic>\n                      -infected cells activate NOD1 signaling within 8\u201312 hours of exposure to the bacterium, roughly coinciding with the microbe\u2019s transition from its infectious to replicative forms. Here, we report that, unlike NOD1 signaling,\n                      <jats:italic toggle=\"yes\">Chlamydia<\/jats:italic>\n                      -induced NOD2 signaling does not occur until later in the pathogen\u2019s developmental cycle. Both\n                      <jats:italic toggle=\"yes\">C. trachomatis<\/jats:italic>\n                      and the related murine pathogen\n                      <jats:italic toggle=\"yes\">Chlamydia muridarum<\/jats:italic>\n                      signal late in infection in HEK293 reporter cell lines expressing either human or murine-derived NOD2 receptors. NOD2 signaling can be modulated by disruption of the chlamydial amidase enzyme, AmiA\n                      <jats:sub>CT<\/jats:sub>\n                      , interrupting the microbe\u2019s developmental cycle, and treatment with inhibitors of lipooligosaccharide or PG biosynthesis\/assembly. These results mirror prior observations with Chlamydia-induced TLR9 signaling, leading us to hypothesize that Chlamydia-induced NOD2 signaling results from lytic events that occur sporadically during the transition between the pathogen\u2019s developmental forms. Given our finding that pre-treating cells with NOD2-stimulatory ligands reduces chlamydial inclusion size and delays the developmental cycle, we hypothesize that the microbe preferentially degrades its PG during development to reduce the generation of NOD2 ligands.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00472-25","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T14:02:06Z","timestamp":1766152926000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["<i>Chlamydia trachomatis<\/i>\n                    restricts signaling through NOD2 until late in the pathogen\u2019s developmental cycle"],"prefix":"10.1128","volume":"94","author":[{"given":"Grace","family":"Overman","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04r3kq386","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Uniformed Services University","place":["Bethesda, USA"]},{"name":"Henry Jackson Foundation for the Advancement of Military Medicine","place":["Bethesda, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Loeckener","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/041nas322","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Pharmaceutical Microbiology, University of Bonn","place":["Bonn, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Williford","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04r3kq386","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Uniformed Services University","place":["Bethesda, USA"]},{"name":"Henry Jackson Foundation for the Advancement of Military Medicine","place":["Bethesda, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung","family":"Davis","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04r3kq386","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Uniformed Services University","place":["Bethesda, USA"]},{"name":"Henry Jackson Foundation for the Advancement of Military Medicine","place":["Bethesda, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aissata","family":"Diallo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04r3kq386","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Uniformed Services University","place":["Bethesda, USA"]},{"name":"Henry Jackson Foundation for the Advancement of Military Medicine","place":["Bethesda, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josie","family":"Blair","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04r3kq386","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Uniformed Services University","place":["Bethesda, USA"]},{"name":"Henry Jackson Foundation for the Advancement of Military Medicine","place":["Bethesda, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9783-8157","authenticated-orcid":false,"given":"Beate","family":"Henrichfreise","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/041nas322","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Pharmaceutical Microbiology, University of Bonn","place":["Bonn, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3028-8474","authenticated-orcid":true,"given":"George W.","family":"Liechti","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04r3kq386","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Uniformed Services University","place":["Bethesda, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0143304"},{"key":"e_1_3_3_3_2","first-page":"363","volume-title":"WHO alliance for the global elimination of trachoma: progress report on elimination of trachoma, 2023","author":"World Health Organization","year":"2024","unstructured":"World Health Organization. 2024. 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