Journal
INFECTION AND IMMUNITY
Volume 73, Issue 4, Pages 2012-2019Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/IAI.73.4.2012-2019.2005
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Funding
- NHLBI NIH HHS [R01 HL059842, HL059842] Funding Source: Medline
- NIAID NIH HHS [AI033774, AI052733-02, AI033142, R01 AI052733, R01 AI033774, R37 AI033142, R01 AI033142] Funding Source: Medline
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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.neofonnans 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.
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