{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T07:05:37Z","timestamp":1790406337164,"version":"4.1.0"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:00:00Z","timestamp":1472688000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:named-content content-type=\"genus-species\">Coxiella burnetii<\/jats:named-content>is a Gram-negative bacterium that causes Q fever in humans. Q fever is an atypical pneumonia transmitted through inhalation of contaminated aerosols. In mammalian lungs,<jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>infects and replicates in several cell types, including alveolar macrophages (AMs). The innate immunity and signaling pathways operating during infection are still poorly understood, in part because of the lack of relevant host cell models for infection<jats:italic>in vitro<\/jats:italic>. In the study described here, we investigated and characterized the infection of primary murine AMs by<jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>phase II<jats:italic>in vitro<\/jats:italic>. Our data reveal that AMs show a pronounced M2 polarization and are highly permissive to<jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>multiplication<jats:italic>in vitro<\/jats:italic>. Murine AMs present an increased susceptibility to infection in comparison to primary bone marrow-derived macrophages. AMs support more than 2 logs of bacterial replication during 12 days of infection in culture, similar to highly susceptible host cells, such as Vero and THP-1 cells. As a proof of principle that AMs are useful for investigation of<jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>replication, we performed experiments with AMs from<jats:italic>Nos2<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>or<jats:italic>Ifng<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>mice. In the absence of gamma interferon and nitric oxide synthase 2 (NOS2), AMs were significantly more permissive than wild-type cells. In contrast, AMs from<jats:italic>Il4<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>mice were more restrictive to<jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>replication, supporting the importance of M2 polarization for the permissiveness of AMs to<jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>replication. Collectively, our data account for understanding the high susceptibility of alveolar macrophages to bacterial replication and support the use of AMs as a relevant model of<jats:named-content content-type=\"genus-species\">C. burnetii<\/jats:named-content>growth in primary macrophages.<\/jats:p>","DOI":"10.1128\/iai.00411-16","type":"journal-article","created":{"date-parts":[[2016,6,14]],"date-time":"2016-06-14T02:29:34Z","timestamp":1465871374000},"page":"2439-2448","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":30,"title":["Murine Alveolar Macrophages Are Highly Susceptible to Replication of Coxiella burnetii Phase II<i>In Vitro<\/i>"],"prefix":"10.1128","volume":"84","author":[{"given":"Talita D.","family":"Fernandes","sequence":"first","affiliation":[{"name":"Department of Cell Biology, School of Medicine of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, FMRP\/USP, Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa D.","family":"Cunha","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, School of Medicine of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, FMRP\/USP, Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana M.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, School of Medicine of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, FMRP\/USP, Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana M.","family":"Massis","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, School of Medicine of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, FMRP\/USP, Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djalma S.","family":"Lima-Junior","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, School of Medicine of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, FMRP\/USP, Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9240-2001","authenticated-orcid":false,"given":"Hayley J.","family":"Newton","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7856-7512","authenticated-orcid":false,"given":"Dario S.","family":"Zamboni","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, School of Medicine of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, FMRP\/USP, Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0950268814003689"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.56.7.1792-1799.1988"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.11.6026-6033.1999"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054566"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12432"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00406-10"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(02)01577-0"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.3.1225-1233.2003"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.4.2075-2080.2004"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00594-07"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12096"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0051941"},{"key":"e_1_3_2_14_2","first-page":"273","article-title":"Induced production of nitric oxide and sensitivity of alveolar macrophages derived from mice with different sensitivity to Coxiella burnetii","volume":"43","author":"Yoshiie K","year":"1999","unstructured":"Yoshiie K, Matayoshi S, Fujimura T, Maeno N, Oda H. 1999. 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