{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T13:38:02Z","timestamp":1786541882172,"version":"build-2736575974"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,8,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Correlates that predict protection against intracellular pathogens, including the highly pathogenic bacterium\n                      <jats:italic toggle=\"yes\">Francisella<\/jats:italic>\n                      , are of interest to evaluate novel candidate vaccines and to facilitate clinical trials. We have previously established an\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      co-culture assay that measures the control of intramacrophage bacterial replication by immune T cells and serves as a functional correlate. Moreover, this assay is a tool to identify additional molecular correlates of protection and to better understand protective T cell responses against\n                      <jats:italic toggle=\"yes\">Francisella<\/jats:italic>\n                      . To study the role of metabolic shifts in protective T cell responses, we used co-cultures to profile the metabolic activities of macrophages and lymphocytes from mice vaccinated with\n                      <jats:italic toggle=\"yes\">F. tularensis<\/jats:italic>\n                      Live Vaccine Strain (LVS). Previous studies indicated that LVS infection of macrophages dysregulates macrophage metabolism and limits glycolysis. Here, we show that co-cultures of LVS-infected macrophages with LVS-primed lymphocytes, which controlled intramacrophage bacterial growth, exhibited more glycolysis than co-cultures containing na\u00efve cells. Further, LVS-primed lymphocytes exhibited a significant loss of respiratory capacity over time, consistent with a transition to an effector T cell state. Gene expression analyses of splenic T cells recovered from co-cultures revealed a set of metabolic genes that were not only upregulated in glycolytic LVS-primed T cells but could also be detected in total primed splenocytes and peripheral blood lymphocytes. Taken together, we find that LVS-primed effector T cells override bacterial-induced metabolic dysregulation in macrophages to control bacterial infection. These results support future studies exploring the use of metabolic intermediates as potential correlates of protection.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Currently, there are no licensed vaccines against the deadly bacterium\n                        <jats:italic toggle=\"yes\">Francisella tularensis<\/jats:italic>\n                        , which causes the disease called tularemia in people and in many animals.\n                        <jats:italic toggle=\"yes\">F. tularensis<\/jats:italic>\n                        is also a potential bioterrorism agent. In this study, we showed that metabolic activity measurements of cells from mice immunized with a candidate tularemia vaccine correlated well with protection against disease. These results suggest a new approach to developing lab tests that can predict successful vaccination before undertaking a clinical trial.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01133-26","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T13:01:05Z","timestamp":1785157265000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["<i>Francisella<\/i>\n                    -primed T cells shift toward glycolysis during control of intramacrophage bacterial growth"],"prefix":"10.1128","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3558-0140","authenticated-orcid":true,"given":"Lara R.","family":"Mittereder","sequence":"first","affiliation":[{"name":"Laboratory of Mucosal Pathogens and Cellular Immunology Office of Vaccines Research and Review Center for Biologics Evaluation and 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