{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T23:59:04Z","timestamp":1762300744510,"version":"3.41.2"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/AuthorWarrantyLicense.v1"},{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"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":["Microbiol Spectr"],"published-print":{"date-parts":[[2024,8,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Traditionally, successful vaccines rely on specific adaptive immunity by activating lymphocytes with an attenuated pathogen, or pathogen subunit, to elicit heightened responses upon subsequent exposures. However, recent work with\n              <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n              and other pathogens has identified a role for \u201ctrained\u201d monocytes in protection through memory-like but non-specific immunity. Here, we used an\n              <jats:italic>in vitro<\/jats:italic>\n              co-culture approach to study the potential role of trained macrophages, including lung alveolar macrophages, in immune responses to the Live Vaccine Strain (LVS) of\n              <jats:italic>Francisella tularensis. F. tularensis<\/jats:italic>\n              is an intracellular bacterium that replicates within mammalian macrophages and causes respiratory as well as systemic disease. We vaccinated mice with\n              <jats:italic>F. tularensis<\/jats:italic>\n              LVS and then obtained lung alveolar macrophages, or derived macrophages from bone marrow. LVS infected and replicated comparably in both types of macrophages, whether na\u00efve or from LVS-vaccinated mice. LVS-infected macrophages were then co-cultured with either na\u00efve splenocytes, splenocytes from mice vaccinated intradermally, or splenocytes from mice vaccinated intravenously. For the first time, we show that immune (but not na\u00efve) splenocytes controlled bacterial replication within alveolar macrophages, similar to previous results using bone marrow-derived macrophage. However, no differences in control of intramacrophage bacterial replication were found between co-cultures with na\u00efve macrophages or macrophages from LVS-vaccinated mice; furthermore, nitric oxide levels and interferon-gamma production in supernatants were largely comparable across all conditions. Thus, in the context of\n              <jats:italic>in vitro<\/jats:italic>\n              co-cultures, the data do not support development of trained macrophages in bone marrow or lungs of mice vaccinated with LVS intradermally or intravenously.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              The discovery of non-specific \u201ctrained immunity\u201d in monocytes has generated substantial excitement. However, to date, training has been studied with relatively few microbes (e.g.,\n              <jats:italic>Mycobacterium bovis<\/jats:italic>\n              Bacille Calmette-Gu\u00e9rin, a live attenuated intracellular bacterium used as a vaccine) and microbial substances (e.g., LPS), and it remains unclear whether training during infection is common. We previously demonstrated that vaccination of mice with\n              <jats:italic>Francisella tularensis<\/jats:italic>\n              Live Vaccine Strain (LVS), another live attenuated intracellular bacterium, protected against challenge with the unrelated bacterium\n              <jats:italic>Listeria monocytogenes<\/jats:italic>\n              . The present study therefore tested whether LVS vaccination engenders trained macrophages that contributed to this protection. To do so, we used a previous\n              <jats:italic>in vitro<\/jats:italic>\n              co-culture approach with murine bone marrow-derived macrophages to expand and study lung alveolar macrophages. We demonstrated that alveolar macrophages can be productively infected and employed to characterize interactions with LVS-immune lymphocytes. However, we find no evidence that either bone marrow-derived or alveolar macrophages are trained by LVS vaccination.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.00028-24","type":"journal-article","created":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T13:02:35Z","timestamp":1719579755000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["<i>Francisella tularensis<\/i>\n            Live Vaccine Strain training of murine alveolar and bone marrow-derived macrophages"],"prefix":"10.1128","volume":"12","author":[{"given":"Hamda","family":"Khan","sequence":"first","affiliation":[{"name":"Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Varunika","family":"Bhargava","sequence":"additional","affiliation":[{"name":"Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8779-8657","authenticated-orcid":true,"given":"Karen L.","family":"Elkins","sequence":"additional","affiliation":[{"name":"Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, 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