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Microarray methods were used to examine differential gene expression in the lungs of C57BL\/6 and CD40 ligand knockout (CD40L-KO) mice over time following exposure to Pneumocystis murina. Immunocompetent C57BL\/6 mice, which control and clear infection efficiently, showed a robust response to infection characterized by the up-regulation of 349 primarily immune response-associated genes. Temporal changes in the expression of these genes identified an early (Week 2), primarily innate response, which waned before the infection was controlled; this was followed by primarily adaptive immune responses that peaked at Week 5, which coincided with clearance of the infection. In conjunction with the latter, there was an increased expression of B cell-associated (Ig) genes at Week 6 that persisted through 11 weeks. In contrast, CD40L-KO mice, which are highly susceptible to developing severe Pneumocystis pneumonia, showed essentially no up-regulation of immune response-associated genes at Days 35\u201375. Immunohistochemical staining supported these observations by demonstrating an increase in CD4+, CD68+, and CD19+ cells in C57BL\/6 but not CD40L-KO mice. Thus, the healthy host demonstrates a robust, biphasic response to infection by Pneumocystis; CD40L is an essential upstream regulator of the adaptive immune responses that efficiently control infection and prevent development of progressive pneumonia.<\/jats:p>","DOI":"10.1189\/jlb.1207816","type":"journal-article","created":{"date-parts":[[2008,5,8]],"date-time":"2008-05-08T21:36:05Z","timestamp":1210282565000},"page":"420-430","source":"Crossref","is-referenced-by-count":37,"title":["Immune responses to\n                    <i>Pneumocystis murina<\/i>\n                    are robust in healthy mice but largely absent in CD40 ligand-deficient mice"],"prefix":"10.1093","volume":"84","author":[{"given":"Beatriz","family":"Hernandez-Novoa","sequence":"first","affiliation":[{"name":"Critical Care Medicine Department, National Institutes of Health Clinical Center, National Institutes of Health , Bethesda, Maryland , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Bishop","sequence":"additional","affiliation":[{"name":"Critical Care Medicine Department, National Institutes of Health Clinical Center, National Institutes of Health , Bethesda, Maryland , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolea","family":"Logun","sequence":"additional","affiliation":[{"name":"Critical Care Medicine Department, National Institutes of Health Clinical Center, National Institutes of Health , Bethesda, Maryland , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J","family":"Munson","sequence":"additional","affiliation":[{"name":"Mathematical and Statistical Computing Laboratory, Division of Computational Bioscience, Center for Information Technology, National Institutes of Health , Bethesda, Maryland , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eldad","family":"Elnekave","sequence":"additional","affiliation":[{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, Maryland , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoila G","family":"Rangel","sequence":"additional","affiliation":[{"name":"Mathematical and Statistical Computing Laboratory, Division of Computational Bioscience, Center for Information Technology, National Institutes of Health , Bethesda, Maryland , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Barb","sequence":"additional","affiliation":[{"name":"Mathematical and Statistical Computing Laboratory, Division of Computational Bioscience, Center for Information Technology, National Institutes of Health , Bethesda, Maryland , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L","family":"Danner","sequence":"additional","affiliation":[{"name":"Critical Care Medicine Department, National Institutes of Health Clinical Center, National Institutes of Health , Bethesda, Maryland , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph A","family":"Kovacs","sequence":"additional","affiliation":[{"name":"Critical Care Medicine Department, National Institutes of Health Clinical Center, National Institutes of Health , Bethesda, Maryland , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,5,8]]},"reference":[{"key":"2023032712471835900_","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1001\/jama.286.19.2450","article-title":"New insights into transmission, diagnosis, and drug treatment of Pneumocystis carinii pneumonia","volume":"286","author":"Kovacs","year":"2001","journal-title":"JAMA"},{"key":"2023032712471835900_","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1086\/375354","article-title":"Quantitation of anti-Pneumocystis jiroveci antibodies in healthy persons and immunocompromised patients","volume":"187","author":"Bishop","year":"2003","journal-title":"J. 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