{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:44:25Z","timestamp":1790502265612,"version":"4.1.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T00:00:00Z","timestamp":1639958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Q fever, a zoonosis caused by <jats:italic>Coxiella burnetii<\/jats:italic>, affects more males than females despite a similar level of exposure. A protective role of estradiol has been reported in mice, suggesting that sex hormones are involved in <jats:italic>C. burnetii<\/jats:italic> infection. We wondered whether the responses of monocytes and monocyte-derived macrophages (MDMs) to <jats:italic>C. burnetii<\/jats:italic> are influenced by sex hormones.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>The bacterial intracellular fate in monocytes was studied using quantitative PCR, and monocyte cytokine production in response to <jats:italic>C. burnetii<\/jats:italic> was assessed using qRT-PCR and immunoassays. Before infection, MDMs from males and females were incubated with testosterone and estradiol, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Bacterial uptake and persistence were similar in monocytes from males and females but were slightly increased in male MDMs. The expression of inflammatory genes, including those encoding TNF and CXCL10, was higher in MDMs from females than in MDMs from males infected by <jats:italic>C. burnetii<\/jats:italic>. Adding testosterone to male MDMs amplified their immunoregulatory properties, including increased expression of <jats:italic>IL10<\/jats:italic> and <jats:italic>TGFB<\/jats:italic> genes and TGF-\u03b2 production in response to <jats:italic>C. burnetii.<\/jats:italic> In contrast, adding estradiol to MDMs from females had no effect on their inflammatory profile.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The stronger inflammatory profile of macrophages from females may have a protective role, likely under estrogen control, while testosterone may affect disease progression by promoting an anti-inflammatory response. This finding may have consequences for personalized management of patients with Q fever.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.705088","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T05:26:47Z","timestamp":1639978007000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Impact of Sex Hormones on Macrophage Responses to Coxiella burnetii"],"prefix":"10.3389","volume":"12","author":[{"given":"Laetitia","family":"Gay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9a","family":"Melenotte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Lopez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit","family":"Desnues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Didier","family":"Raoult","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Leone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soraya","family":"Mezouar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Louis","family":"Mege","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00045-16","article-title":"From Q Fever to Coxiella Burnetii Infection: A Paradigm Change","volume":"30","author":"Eldin","year":"2017","journal-title":"Clin Microbiol Rev"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e181580","DOI":"10.1001\/jamanetworkopen.2018.1580","article-title":"Clinical Features and Complications of Coxiella Burnetii Infections From the French National Reference Center for Q Fever","volume":"1","author":"Melenotte","year":"2018","journal-title":"JAMA Netw Open"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(92)90173-9","article-title":"Epidemiologic Features and Clinical Presentation of Acute Q Fever in Hospitalized Patients: 323 French Cases","volume":"93","author":"Dupont","year":"1992","journal-title":"Am J Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1016\/j.cmi.2019.02.030","article-title":"The Sexual Dimorphism of Anticardiolipin Autoantibodies in Acute Q Fever Patients","volume":"25","author":"Melenotte","year":"2019","journal-title":"Clin Microbiol Infect"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1097\/01.md.0000165658.82869.17","article-title":"Blood Culture-Negative Endocarditis in a Reference Center: Etiologic Diagnosis of 348 Cases","volume":"84","author":"Houpikian","year":"2005","journal-title":"Med (Baltimore)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmni.2018.05.010","article-title":"Sex and Bacterial Infectious Diseases","volume":"26","author":"M\u00e8ge","year":"2018","journal-title":"N Microbes New Infect"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1385\/IR:34:3:177","article-title":"Sexual Dimorphism in Innate Immune Responses to Infectious Organisms","volume":"34","author":"Marriott","year":"2006","journal-title":"Immunol Res"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(02)00440-1","article-title":"Raoult D. 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