{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:34:13Z","timestamp":1790703253786,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009493","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T00:00:00Z","timestamp":1633392000000}}],"reference-count":79,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T00:00:00Z","timestamp":1632355200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA188034"],"award-info":[{"award-number":["R01CA188034"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI077600"],"award-info":[{"award-number":["R01AI077600"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32AI55397"],"award-info":[{"award-number":["T32AI55397"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["DGE-1747503"],"award-info":[{"award-number":["DGE-1747503"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Listeria monocytogenes<\/jats:italic>is an intracellular bacterium that elicits robust CD8<jats:sup>+<\/jats:sup>T-cell responses. Despite the ongoing development of<jats:italic>L<\/jats:italic>.<jats:italic>monocytogenes<\/jats:italic>-based platforms as cancer vaccines, our understanding of how<jats:italic>L<\/jats:italic>.<jats:italic>monocytogenes<\/jats:italic>drives robust CD8<jats:sup>+<\/jats:sup>T-cell responses remains incomplete. One overarching hypothesis is that activation of cytosolic innate pathways is critical for immunity, as strains of<jats:italic>L<\/jats:italic>.<jats:italic>monocytogenes<\/jats:italic>that are unable to access the cytosol fail to elicit robust CD8<jats:sup>+<\/jats:sup>T-cell responses and in fact inhibit optimal T-cell priming. Counterintuitively, however, activation of known cytosolic pathways, such as the inflammasome and type I IFN, lead to impaired immunity. Conversely, production of prostaglandin E<jats:sub>2<\/jats:sub>(PGE<jats:sub>2<\/jats:sub>) downstream of cyclooxygenase-2 (COX-2) is essential for optimal<jats:italic>L<\/jats:italic>.<jats:italic>monocytogenes<\/jats:italic>T-cell priming. Here, we demonstrate that vacuole-constrained<jats:italic>L<\/jats:italic>.<jats:italic>monocytogenes<\/jats:italic>elicit reduced PGE<jats:sub>2<\/jats:sub>production compared to wild-type strains in macrophages and dendritic cells<jats:italic>ex vivo<\/jats:italic>.<jats:italic>In vivo<\/jats:italic>, infection with wild-type<jats:italic>L<\/jats:italic>.<jats:italic>monocytogenes<\/jats:italic>leads to 10-fold increases in PGE<jats:sub>2<\/jats:sub>production early during infection whereas vacuole-constrained strains fail to induce PGE<jats:sub>2<\/jats:sub>over mock-immunized controls. Mice deficient in COX-2 specifically in Lyz2<jats:sup>+<\/jats:sup>or CD11c<jats:sup>+<\/jats:sup>cells produce less PGE<jats:sub>2<\/jats:sub>, suggesting these cell subsets contribute to PGE<jats:sub>2<\/jats:sub>levels<jats:italic>in vivo<\/jats:italic>, while depletion of phagocytes with clodronate abolishes PGE<jats:sub>2<\/jats:sub>production completely. Taken together, this work demonstrates that optimal PGE<jats:sub>2<\/jats:sub>production by phagocytes depends on<jats:italic>L<\/jats:italic>.<jats:italic>monocytogenes<\/jats:italic>access to the cytosol, suggesting that one reason cytosolic access is required to prime CD8<jats:sup>+<\/jats:sup>T-cell responses may be to facilitate production of PGE<jats:sub>2<\/jats:sub>.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009493","type":"journal-article","created":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T11:25:03Z","timestamp":1632482703000},"page":"e1009493","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Phagocytes produce prostaglandin E2 in response to cytosolic Listeria monocytogenes"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1607-5931","authenticated-orcid":true,"given":"Courtney 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M.","family":"Stevenson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3568-3070","authenticated-orcid":true,"given":"Daniel","family":"Amador-Noguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5676-389X","authenticated-orcid":true,"given":"Mark J.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9367-794X","authenticated-orcid":true,"given":"John-Demian","family":"Sauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,9,23]]},"reference":[{"key":"ppat.1009493.ref001","doi-asserted-by":"crossref","first-page":"376","DOI":"10.4049\/jimmunol.160.1.376","article-title":"Chronic Listeria infection in SCID mice: 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