{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T20:22:52Z","timestamp":1783974172597,"version":"3.55.0"},"reference-count":39,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"University of Texas at San Antonio","doi-asserted-by":"publisher","award":["AI123464"],"award-info":[{"award-number":["AI123464"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"University of Texas at San Antonio","doi-asserted-by":"publisher","award":["AI133023"],"award-info":[{"award-number":["AI133023"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Coxiella burnetii, the causative agent of human Q fever, subverts macrophage antimicrobial functions to establish an intracellular replicative niche. To better understand host\u2013pathogen interactions, we investigated the transcriptional responses of human alveolar macrophages (hAMs) infected with virulent [NMI, G (Q212)], attenuated (NMII), and avirulent (Dugway) strains of C. burnetii. RNA sequencing indicated that all strains activated proinflammatory pathways, particularly IL-17 signaling, though the magnitude and nature of the response varied by strain. Infections with NMI, NMII or G (Q212) resulted in differential expression of roughly the same number of genes, while Dugway infection induced a stronger transcriptional response. Dugway and G (Q212) tended to polarize macrophages toward M1-like states, whereas responses to NMI and NMII were variable. Cytokine assays of NMII-infected THP-1 macrophages suggested the activation of IL-17 signaling, but only at later stages of infection, and single-cell RNA sequencing of NMII-infected THP-1 macrophages indicated heterogeneity in host response to infection, with distinct subpopulations exhibiting M1-like and M2-like inflammatory profiles. These findings highlight the complexity of macrophage response to C. burnetii 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.<\/jats:p>","DOI":"10.3390\/pathogens14111101","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T17:38:22Z","timestamp":1761759502000},"page":"1101","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Coxiella burnetii Strains Elicit Distinct Inflammatory Responses in Human Macrophages"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0309-8069","authenticated-orcid":false,"given":"Madhur","family":"Sachan","sequence":"first","affiliation":[{"name":"Department of Medicine, Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Dragan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4385-1318","authenticated-orcid":false,"given":"Het","family":"Adhvaryu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E.","family":"Voth","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Raghavan","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, The University of Texas at San Antonio, San Antonio, TX 78249, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1111\/cmi.12096","article-title":"Virulent Coxiella burnetii pathotypes productively infect primary human alveolar macrophages","volume":"15","author":"Graham","year":"2013","journal-title":"Cell. 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