{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:54:38Z","timestamp":1768510478722,"version":"3.49.0"},"posted":{"date-parts":[[2024,2,3]]},"group-title":"Microbiology","reference-count":104,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,2,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:italic>Coxiella burnetii<\/jats:italic>\n                  is an obligate intracellular bacteria which causes the global zoonotic disease Q Fever. Treatment options for infection are limited, and development of novel therapeutic strategies requires a greater understanding of how\n                  <jats:italic>C. burnetii<\/jats:italic>\n                  interacts with immune signaling. Cell death responses are known to be manipulated by\n                  <jats:italic>C. burnetii<\/jats:italic>\n                  , but the role of caspase-8, a central regulator of multiple cell death pathways, has not been investigated. In this research, we studied bacterial manipulation of caspase-8 signaling and the significance of caspase-8 to\n                  <jats:italic>C. burnetii<\/jats:italic>\n                  infection, examining bacterial replication, cell death induction, and cytokine signaling. We measured caspase, RIPK, and MLKL activation in\n                  <jats:italic>C. burnetii<\/jats:italic>\n                  -infected TNF\u03b1\/CHX-treated THP-1 macrophage-like cells and TNF\u03b1\/ZVAD-treated L929 cells to assess apoptosis and necroptosis signaling. Additionally, we measured\n                  <jats:italic>C. burnetii<\/jats:italic>\n                  replication, cell death, and TNF\u03b1 induction over 12 days in RIPK1-kinase-dead, RIPK3-kinase-dead, or RIPK3-kinase-dead-caspase-8\n                  <jats:sup>-\/-<\/jats:sup>\n                  BMDMs to understand the significance of caspase-8 and RIPK1\/3 during infection. We found that caspase-8 is inhibited by\n                  <jats:italic>C. burnetii<\/jats:italic>\n                  , coinciding with inhibition of apoptosis and increased susceptibility to necroptosis. Furthermore,\n                  <jats:italic>C. burnetii<\/jats:italic>\n                  replication was increased in BMDMs lacking caspase-8, but not in those lacking RIPK1\/3 kinase activity, corresponding with decreased TNF\u03b1 production and reduced cell death. As TNF\u03b1 is associated with the control of\n                  <jats:italic>C. burnetii<\/jats:italic>\n                  , this lack of a TNF\u03b1 response may allow for the unchecked bacterial growth we saw in caspase-8\n                  <jats:sup>-\/-<\/jats:sup>\n                  BMDMs. This research identifies and explores caspase-8 as a key regulator of\n                  <jats:italic>C. burnetii<\/jats:italic>\n                  infection, opening novel therapeutic doors.\n                <\/jats:p>","DOI":"10.1101\/2024.02.02.578698","type":"posted-content","created":{"date-parts":[[2024,2,4]],"date-time":"2024-02-04T00:10:10Z","timestamp":1707005410000},"source":"Crossref","is-referenced-by-count":1,"title":["Caspase-8 activity mediates TNF\u03b1 production and restricts\n                  <i>Coxiella burnetii<\/i>\n                  replication during murine macrophage infection"],"prefix":"10.64898","author":[{"given":"Chelsea A.","family":"Osbron","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Crystal","family":"Lawson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nolan","family":"Hanna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather S.","family":"Koehler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6394-332X","authenticated-orcid":false,"given":"Alan G.","family":"Goodman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024020612200688000_2024.02.02.578698v1.1","doi-asserted-by":"publisher","DOI":"10.2307\/4582746"},{"key":"2024020612200688000_2024.02.02.578698v1.2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/5.4.790"},{"key":"2024020612200688000_2024.02.02.578698v1.3","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00045-16"},{"key":"2024020612200688000_2024.02.02.578698v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(05)70052-9"},{"key":"2024020612200688000_2024.02.02.578698v1.5","first-page":"1","article-title":"Diagnosis and management of Q fever--United States, 2013: recommendations from CDC and the Q Fever Working Group","volume":"62","year":"2013","journal-title":"MMWR Recomm Rep Morb Mortal Wkly Rep Recomm Rep"},{"key":"2024020612200688000_2024.02.02.578698v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(03)00804-1"},{"key":"2024020612200688000_2024.02.02.578698v1.7","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.024778-0"},{"key":"2024020612200688000_2024.02.02.578698v1.8","doi-asserted-by":"crossref","unstructured":"Morse SA , Quigley BR. 2020. 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