{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:17:17Z","timestamp":1790371037391,"version":"4.1.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2000,3,1]],"date-time":"2000-03-01T00:00:00Z","timestamp":951868800000},"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":[[2000,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Innate immunity plays an important role in pulmonary host defense against Pneumocystis carinii, an important pathogen in individuals with impaired cell-mediated immunity. We investigated the role of GM-CSF in host defense in a model of P. carinii pneumonia induced by intratracheal inoculation of CD4-depleted mice. Lung GM-CSF levels increased progressively during the infection and were significantly greater than those in uninfected controls 3, 4, and 5 wk after inoculation. When GM-CSF gene-targeted mice (GM\u2212\/\u2212) depleted of CD4+ cells were inoculated with P. carinii, the intensities of infection and inflammation were increased significantly compared with those in CD4-depleted wild-type mice. In contrast, transgenic expression of GM-CSF directed solely in the lungs of GM\u2212\/\u2212 mice (using the surfactant protein C promoter) dramatically decreased the intensity of infection and inflammation 4 wk after inoculation. The concentrations of surfactant proteins A and D were greater in both uninfected and infected GM\u2212\/\u2212 mice compared with those in wild-type controls, suggesting that this component of the innate response was preserved in the GM\u2212\/\u2212 mice. However, alveolar macrophages (AM) from GM\u2212\/\u2212 mice demonstrated impaired phagocytosis of purified murine P. carinii organisms in vitro compared with AM from wild-type mice. Similarly, AM production of TNF-\u03b1 in response to P. carinii in vitro was totally absent in AM from GM\u2212\/\u2212 mice, while GM-CSF-replete mice produced abundant TNF in this setting. Thus, GM-CSF plays a critical role in the inflammatory response to P. carinii in the setting of impaired cell-mediated immunity through effects on AM activation.<\/jats:p>","DOI":"10.4049\/jimmunol.164.5.2602","type":"journal-article","created":{"date-parts":[[2014,4,21]],"date-time":"2014-04-21T19:48:34Z","timestamp":1398109714000},"page":"2602-2609","source":"Crossref","is-referenced-by-count":121,"title":["Granulocyte-Macrophage Colony-Stimulating Factor in the Innate Immune Response to\n                    <i>Pneumocystis carinii<\/i>\n                    Pneumonia in Mice"],"prefix":"10.1093","volume":"164","author":[{"suffix":"III","given":"Robert","family":"Paine","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, University of Michigan , Ann Arbor, MI 48105"},{"name":"Department of Veterans Affairs Medical Center , Ann Arbor, MI 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela M","family":"Preston","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, University of Michigan , Ann Arbor, MI 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Wilcoxen","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, University of Michigan , Ann Arbor, MI 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Jin","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, University of Michigan , Ann Arbor, MI 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian B","family":"Siu","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, University of Michigan , Ann Arbor, MI 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan B","family":"Morris","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, University of Michigan , Ann Arbor, MI 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacquelyn A","family":"Reed","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Biology, Children\u2019s Hospital , Cincinnati, OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Ross","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Biology, Children\u2019s Hospital , Cincinnati, OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A","family":"Whitsett","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Biology, Children\u2019s Hospital , Cincinnati, OH 45229"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M","family":"Beck","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, University of Michigan , Ann Arbor, MI 48105"},{"name":"Department of Veterans Affairs Medical Center , Ann Arbor, MI 48105"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2000,3,1]]},"reference":[{"key":"2026020213164893200_R1","first-page":"60","volume-title":"Am. 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