{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T01:32:47Z","timestamp":1768527167744,"version":"3.49.0"},"posted":{"date-parts":[[2025,8,11]]},"group-title":"Microbiology","reference-count":39,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["AI123464, AI133023"],"award-info":[{"award-number":["AI123464, AI133023"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,8,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  <jats:italic>Coxiella burnetii<\/jats:italic>\n                  , the causative agent of human Q fever, subverts macrophage antimicrobial functions to establish an intracellular replicative niche. To better understand the host-pathogen interactions, we investigated the transcriptional responses of human alveolar macrophages (hAMs) infected with virulent (NMI, G), attenuated (NMII), and avirulent (Dugway) strains of\n                  <jats:italic>C. burnetii<\/jats:italic>\n                  . RNA sequencing analysis revealed that all strains activated proinflammatory pathways, particularly IL-17 signaling, though the magnitude and nature of the response varied by strain. Dugway infection induced the most robust transcriptional response and consistent M1-like macrophage polarization, while responses to NMI and NMII were more variable. Cytokine assays confirmed significant secretion of effectors downstream of IL-17 signaling, but only at later stages of infection. Single-cell RNA sequencing further revealed heterogeneity in macrophage response to\n                  <jats:italic>C. burnetii<\/jats:italic>\n                  infection, with distinct subpopulations exhibiting divergent inflammatory profiles. These findings highlight the complexity of macrophage responses to\n                  <jats:italic>C. burnetii<\/jats:italic>\n                  and underscore the importance of strain-specific and cell-specific factors in shaping host immunity. Understanding these dynamics may inform the development of targeted therapies for Q fever.\n                <\/jats:p>","DOI":"10.1101\/2025.08.10.669536","type":"posted-content","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T03:25:13Z","timestamp":1754969113000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>Coxiella burnetii<\/i>\n                  strains elicit distinct inflammatory responses in human macrophages"],"prefix":"10.64898","author":[{"given":"Madhur","family":"Sachan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda","family":"Dragan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Het","family":"Adhvaryu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel E","family":"Voth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rahul","family":"Raghavan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025081319150458000_2025.08.10.669536v1.1","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12096"},{"key":"2025081319150458000_2025.08.10.669536v1.2","doi-asserted-by":"publisher","DOI":"10.1080\/01902140701756562"},{"key":"2025081319150458000_2025.08.10.669536v1.3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004099"},{"key":"2025081319150458000_2025.08.10.669536v1.4","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.05544-11"},{"key":"2025081319150458000_2025.08.10.669536v1.5","first-page":"3360310","article-title":"IL-17: Balancing Protective Immunity and Pathogenesis","volume":"2023","year":"2023","journal-title":"J Immunol Res"},{"key":"2025081319150458000_2025.08.10.669536v1.6","doi-asserted-by":"publisher","DOI":"10.2217\/fmb-2016-0044"},{"key":"2025081319150458000_2025.08.10.669536v1.7","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/nrmicro3049","article-title":"Molecular pathogenesis of the obligate intracellular bacterium Coxiella burnetii","volume":"11","year":"2013","journal-title":"Nat Rev Micro"},{"key":"2025081319150458000_2025.08.10.669536v1.8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2007.00901.x"},{"key":"2025081319150458000_2025.08.10.669536v1.9","doi-asserted-by":"crossref","first-page":"100667","DOI":"10.1016\/j.onehlt.2023.100667","article-title":"A systematic review of global Q fever outbreaks","volume":"18","year":"2024","journal-title":"One Health"},{"key":"2025081319150458000_2025.08.10.669536v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2015.07.011"},{"key":"2025081319150458000_2025.08.10.669536v1.11","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01141-08"},{"key":"2025081319150458000_2025.08.10.669536v1.12","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.49.3.775-779.1985"},{"key":"2025081319150458000_2025.08.10.669536v1.13","doi-asserted-by":"crossref","unstructured":"Tesfamariam M , Binette P , Cockrell D , Beare PA , Heinzen RA , Shaia C , Long CM . 2022. 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