{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:52:29Z","timestamp":1791298349422,"version":"4.1.0"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2008,9,1]],"date-time":"2008-09-01T00:00:00Z","timestamp":1220227200000},"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":[[2008,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Francisella tularensis<\/jats:italic>\n                    , a small gram-negative intracellular bacterium responsible for causing tularemia, is highly pathogenic and classified as a category A agent of bioterrorism. As for other intracellular pathogens, successful protective immune responses to\n                    <jats:italic>Francisella tularensis<\/jats:italic>\n                    require rapid and efficient induction of gamma interferon (IFN-\u03b3) production. Studies using intracellular bacteria such as\n                    <jats:italic>Listeria monocytogenes<\/jats:italic>\n                    as well as\n                    <jats:italic>Francisella<\/jats:italic>\n                    suggest that natural killer (NK) and T cells are important sources of IFN-\u03b3. However, comprehensive characterization of specific sources of IFN-\u03b3 produced during\n                    <jats:italic>Francisella<\/jats:italic>\n                    infection in vivo remains incomplete, and depletion of NK cells before infection of mice with the\n                    <jats:italic>F. tularensis<\/jats:italic>\n                    live vaccine strain (LVS) has little impact on the course or outcome of infection. In this study, we determined the cell subpopulations that respond quickly to intradermal\n                    <jats:italic>F. tularensis<\/jats:italic>\n                    LVS infection of mice by producing IFN-\u03b3 within hours to a few days. Splenic and liver lymphocytes were obtained from LVS-infected mice and analyzed for IFN-\u03b3 mRNA by reverse transcription-PCR, for intracellular cytokine expression by multiparameter flow cytometry, and for ex vivo production of IFN-\u03b3 protein by enzyme-linked immunosorbent assay. Cells producing IFN-\u03b3 were readily detectable by day 3 after infection, and numbers progressively increased through days 5 to 7. Importantly, the cell types responsible for IFN-\u03b3 production were much more varied than expected: these included not only NK cells and T cells, which might be predicted, but also other cells, including dendritic cells (DCs), \u201cNK DCs,\u201d NK T cells, and neutrophils. Most importantly, since RAG-1 knockout mice appeared to exhibit a frequency of IFN-\u03b3-producing cells comparable to that of intact wild-type mice, early IFN-\u03b3 production by innate immune cells does not depend on the presence of T or B cells.\n                  <\/jats:p>","DOI":"10.1128\/iai.00514-08","type":"journal-article","created":{"date-parts":[[2008,6,23]],"date-time":"2008-06-23T20:55:18Z","timestamp":1214254518000},"page":"4311-4321","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":39,"title":["Diverse Myeloid and Lymphoid Cell Subpopulations Produce Gamma Interferon during Early Innate Immune Responses to\n                    <i>Francisella tularensis<\/i>\n                    Live Vaccine Strain"],"prefix":"10.1128","volume":"76","author":[{"given":"Roberto","family":"De Pascalis","sequence":"first","affiliation":[{"name":"Laboratory of Mycobacterial Diseases and Cellular Immunology, Center for Biologics Research and Evaluation, U.S. FDA, 1401 Rockville Pike, HFM 431, Rockville, Maryland 20852"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betsy C.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L.","family":"Elkins","sequence":"additional","affiliation":[{"name":"Laboratory of Mycobacterial Diseases and Cellular Immunology, Center for Biologics Research and Evaluation, U.S. FDA, 1401 Rockville Pike, HFM 431, Rockville, Maryland 20852"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"5600","DOI":"10.4049\/jimmunol.161.10.5600","volume":"161","year":"1998","unstructured":"Andersson, A., W. 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