{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:22:10Z","timestamp":1784784130068,"version":"3.55.0"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2006,6,1]],"date-time":"2006-06-01T00:00:00Z","timestamp":1149120000000},"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":[[2006,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pulmonary infection by\n                    <jats:italic>Yersinia pestis<\/jats:italic>\n                    causes pneumonic plague, a rapidly progressing and often fatal disease. To aid the development of safe and effective pneumonic plague vaccines, we are deciphering mechanisms used by the immune system to protect against lethal pulmonary\n                    <jats:italic>Y. pestis<\/jats:italic>\n                    infection. In murine pneumonic plague models, passive transfer of convalescent-phase sera confers protection, as does active vaccination with live\n                    <jats:italic>Y. pestis<\/jats:italic>\n                    . Here, we demonstrate that protection by either protocol relies upon both gamma interferon (IFN-\u03b3) and tumor necrosis factor alpha (TNF-\u03b1) cytokines classically associated with type 1 cellular immunity. In both protocols, abrogating IFN-\u03b3 or TNF-\u03b1 activity significantly decreases survival and increases the bacterial burden in pulmonary, splenic, and hepatic tissues. Neutralization of either cytokine also counteracts challenge-induced, vaccination-dependent upregulation of nitric oxide synthase 2 (NOS2). Moreover, genetic depletion of NOS2 suppresses protection conferred by serotherapy. We conclude that IFN-\u03b3, TNF-\u03b1, and NOS2, key elements of cellular immunity, perform critical protective functions during humoral defense against lethal pulmonary\n                    <jats:italic>Y. pestis<\/jats:italic>\n                    challenge. These observations strongly suggest that plague vaccines should strive to maximally prime both cellular and humoral immunity.\n                  <\/jats:p>","DOI":"10.1128\/iai.00185-06","type":"journal-article","created":{"date-parts":[[2006,5,19]],"date-time":"2006-05-19T19:52:41Z","timestamp":1148068361000},"page":"3381-3386","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":92,"title":["Gamma Interferon, Tumor Necrosis Factor Alpha, and Nitric Oxide Synthase 2, Key Elements of Cellular Immunity, Perform Critical Protective Functions during Humoral Defense against Lethal Pulmonary\n                    <i>Yersinia pestis<\/i>\n                    Infection"],"prefix":"10.1128","volume":"74","author":[{"given":"Michelle A.","family":"Parent","sequence":"first","affiliation":[{"name":"Trudeau Institute, Saranac Lake, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey B.","family":"Wilhelm","sequence":"additional","affiliation":[{"name":"Trudeau Institute, Saranac Lake, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence W.","family":"Kummer","sequence":"additional","affiliation":[{"name":"Trudeau Institute, Saranac Lake, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank M.","family":"Szaba","sequence":"additional","affiliation":[{"name":"Trudeau Institute, Saranac Lake, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isis K.","family":"Mullarky","sequence":"additional","affiliation":[{"name":"Trudeau Institute, Saranac Lake, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen T.","family":"Smiley","sequence":"additional","affiliation":[{"name":"Trudeau Institute, Saranac Lake, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1998.58.793"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.6.2590-2599.1994"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00191545"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.7.3673-3681.2003"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.2174\/1566524054022567"},{"key":"e_1_3_2_7_2","doi-asserted-by":"crossref","first-page":"348","DOI":"10.4049\/jimmunol.83.4.348","volume":"83","year":"1959","unstructured":"Cavanaugh, D. 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