{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:50:06Z","timestamp":1773661806526,"version":"3.50.1"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2002,1,1]],"date-time":"2002-01-01T00:00:00Z","timestamp":1009843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Urokinase-type plasminogen activator (uPA)\u2212\/\u2212 mice cannot mount protective host defenses during infection with the opportunistic yeast Cryptococcus neoformans (52D). Because effective host defense against C. neoformans requires specific immune responses and the generation of type 1 (T1) cytokines, we determined how the absence of uPA impacts these processes. Wild-type (WT) and uPA\u2212\/\u2212 mice were inoculated with C. neoformans. Macrophage antifungal activity was assessed histologically, T lymphocyte responses in vivo and proliferation in vitro were quantified, and cytokine concentrations were determined by ELISA. uPA\u2212\/\u2212 macrophages have impaired antimicrobial activity. Regional lymph nodes of infected uPA\u2212\/\u2212 mice contained fewer cells than WT, suggesting impaired T cell proliferation in response to the pathogen in vivo. In vitro, uPA\u2212\/\u2212 T lymphocytes had impaired proliferative responses to C. neoformans rechallenge compared with WT. Infected WT mice generated T1 cytokines in the lung, characterized by high levels of IFN-\u03b3 and IL-12. uPA\u2212\/\u2212 mice had decreased levels of IFN-\u03b3 and IL-12, and increased IL-5, a type 2 cytokine. In the absence of uPA, the cytokine profile of regional lymph nodes shifted from a T1 pattern characterized by IFN-\u03b3 and IL-2 to a weak, nonpolarized response. We conclude that in the absence of uPA, lymphocyte proliferative responses are diminished, and mice fail to generate protective T1 cytokines, resulting in impaired antimicrobial activity. This study provides novel evidence that uPA is a critical modulator of immune responses and of immune cell effector functions in vivo.<\/jats:p>","DOI":"10.4049\/jimmunol.168.2.801","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T18:18:01Z","timestamp":1398017881000},"page":"801-809","source":"Crossref","is-referenced-by-count":48,"title":["Urokinase-Type Plasminogen Activator Is Required for the Generation of a Type 1 Immune Response to Pulmonary\n                    <i>Cryptococcus neoformans<\/i>\n                    Infection"],"prefix":"10.1093","volume":"168","author":[{"given":"Margaret R","family":"Gyetko","sequence":"first","affiliation":[{"name":"Pulmonary and Critical Care Medicine Division, Department of Internal Medicine and University of Michigan Medical Center , Ann Arbor, MI 48109"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sudha","family":"Sud","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Medicine Division, Department of Internal Medicine and University of Michigan Medical Center , Ann Arbor, MI 48109"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gwo-Hsiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Medicine Division, Department of Internal Medicine and University of Michigan Medical Center , Ann Arbor, MI 48109"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer A","family":"Fuller","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Medicine Division, Department of Internal Medicine and University of Michigan Medical Center , Ann Arbor, MI 48109"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen W","family":"Chensue","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ann Arbor Veterans Affairs Medical Center and University of Michigan Medical Center , Ann Arbor, MI 48109"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Galen B","family":"Toews","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Medicine Division, Department of Internal Medicine and University of Michigan Medical Center , Ann Arbor, MI 48109"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2002,1,15]]},"reference":[{"key":"2026020208145312500_R1","first-page":"93","volume-title":"Annu. 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