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However, there is also evidence from various systems that melanins have immunomodulatory properties, which conceivably could contribute to virulence by altering immune responses. To investigate the effect of melanin on the immune response, we compared the murine pulmonary responses to infection with melanized and nonmelanized<jats:italic>Cryptococcus neoformans<\/jats:italic>cells. Infection with melanized cells resulted in a greater fungal burden during the early stages of infection and was associated with higher levels of interleukin-4 and MCP-1 and greater numbers of infiltrating leukocytes. Infection with laccase-positive (melanotic)<jats:italic>C. neoformans<\/jats:italic>cells also elicited higher MCP-1 levels and more infiltrating leukocytes than did infection with laccase-negative cells. Melanization interfered with phagocytosis in vivo for encapsulated<jats:italic>C. neoformans<\/jats:italic>but not for nonencapsulated cells. The results provide strong evidence that cryptococcal melanization can influence the immune response to infection and suggest that immunomodulation is an additional mechanism by which the pigment contributes to virulence.<\/jats:p>","DOI":"10.1128\/iai.73.4.2012-2019.2005","type":"journal-article","created":{"date-parts":[[2005,3,22]],"date-time":"2005-03-22T03:57:31Z","timestamp":1111463851000},"page":"2012-2019","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":86,"title":["Melanization of<i>Cryptococcus neoformans<\/i>Affects Lung Inflammatory Responses during Cryptococcal Infection"],"prefix":"10.1128","volume":"73","author":[{"given":"Aron J.","family":"Mednick","sequence":"first","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D.","family":"Nosanchuk","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Casadevall","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine"},{"name":"Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.1.229-237.2004"},{"key":"e_1_3_2_3_2","first-page":"764","volume":"48","year":"1998","unstructured":"Avramidis, N., A. 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