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The objective of this study was to investigate the interaction of macrophages with cells from smooth-colony variants (SM) and mucoid-colony variants (MC) arising from phenotypic switching of<jats:italic>Cryptococcus neoformans<\/jats:italic>. Alveolar macrophages (AMs) isolated from SM- and MC-infected mice exhibited differences in gene and surface expression of PD-L1, PD-L2, and major histocompatibility class II (MHC-II). PD-L1 and PD-L2 are the ligands for PD1 and are differentially regulated in Th1- and Th2-type cells. In addition, macrophage activation in SM- and MC-infected mice was characterized as alternatively activated. Flow cytometric and cytokine analysis demonstrated that MC infection was associated with the emergence of Th17 cells and higher levels of interleukin-17 (IL-17) in lung tissue, which were reduced by AM depletion. In conclusion, our results indicate that macrophages play a significant role in maintaining damage-promoting inflammation in the lung during MC infection, which ultimately results in death.<\/jats:p>","DOI":"10.1128\/iai.01049-09","type":"journal-article","created":{"date-parts":[[2010,1,5]],"date-time":"2010-01-05T02:10:40Z","timestamp":1262657440000},"page":"1049-1057","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":33,"title":["<i>Cryptococcus neoformans<\/i>Variants Generated by Phenotypic Switching Differ in Virulence through Effects on Macrophage Activation"],"prefix":"10.1128","volume":"78","author":[{"given":"A.","family":"Guerrero","sequence":"first","affiliation":[{"name":"Departments of Microbiology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Jain","sequence":"additional","affiliation":[{"name":"Medicine, Albert Einstein College of Medicine, Bronx, New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Wang","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. 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