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Infection and Immunity, April 2005, p. 2012-2019, Vol. 73, No. 4
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.4.2012-2019.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Melanization of Cryptococcus neoformans Affects Lung Inflammatory Responses during Cryptococcal Infection

Division of Infectious Disease, Department of Medicine,¹ Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York²

Received 26 July 2004/ Returned for modification 10 September 2004/ Accepted 30 November 2004

The production of melanin pigments is associated with virulence for many microbes. Melanin is believed to contribute to microbial virulence by protecting microbial cells from oxidative attack during infection. 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 Cryptococcus neoformans 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) C. neoformans 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 C. neoformans 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.

Editor: T. R. Kozel

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• Nosanchuk, J. D., Casadevall, A. (2006). Impact of Melanin on Microbial Virulence and Clinical Resistance to Antimicrobial Compounds. Antimicrob. Agents Chemother. 50: 3519-3528 [Full Text]  
• Heung, L. J., Kaiser, A. E., Luberto, C., Del Poeta, M. (2005). The Role and Mechanism of Diacylglycerol-Protein Kinase C1 Signaling in Melanogenesis by Cryptococcus neoformans. J. Biol. Chem. 280: 28547-28555 [Abstract] [Full Text]