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Infection and Immunity, June 2008, p. 2362-2367, Vol. 76, No. 6
0019-9567/08/$08.00+0     doi:10.1128/IAI.00095-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Role of the Mannose Receptor in a Murine Model of Cryptococcus neoformans Infection

Jennifer M. Dan,^1,2 Ryan M. Kelly,^1, Chrono K. Lee,² and Stuart M. Levitz^1,2*

Department of Microbiology and Immunology Training Program, Boston University School of Medicine, Boston, Massachusetts 02118,¹ Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605²

Received 23 January 2008/ Returned for modification 2 March 2008/ Accepted 27 March 2008

Cryptococcus neoformans is an encapsulated fungal pathogen with a predilection to infect persons with suppressed T-cell function. Cryptococcal mannoproteins (MP) are highly mannosylated antigens which elicit T-cell responses in infected mice and in convalescent patients. Key to the immunogenicity of MP is its capacity to bind to the conserved mannose receptor (MR), CD206, on dendritic cells (DCs). To test the role of the MR in the immune response to C. neoformans, wild-type and MR knockout (MR KO) mice were compared by using in vivo and ex vivo models of cryptococcosis. Following a pulmonary challenge with C. neoformans, MR KO mice died significantly faster than wild-type mice and had higher lung fungal burdens after 4 weeks of infection. Uptake of MP was similar when DCs obtained from wild-type and MR KO mice were compared. Additionally, MP did not upregulate the maturation markers major histocompatibility complex class II, CD86, and CD40 in either wild-type or MR KO DCs. However, MP stimulated lymphoproliferation in CD4⁺ T cells obtained from the peripheral lymph nodes of infected wild-type but not MR KO mice. These studies demonstrate a nonredundant role for the MR in the development of CD4⁺ T-cell responses to MP and protection from C. neoformans.

Published ahead of print on 7 April 2008.

Editor: A. Casadevall

Present address: Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455.