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Infection and Immunity, October 2009, p. 4284-4294, Vol. 77, No. 10
0019-9567/09/$08.00+0     doi:10.1128/IAI.00628-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Cryptococcus gattii Isolates from the British Columbia Cryptococcosis Outbreak Induce Less Protective Inflammation in a Murine Model of Infection than Cryptococcus neoformans{triangledown} ,{dagger}

Po-Yan Cheng, Anita Sham, and James W. Kronstad*

The Michael Smith Laboratories, Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4

Received 2 June 2009/ Returned for modification 11 July 2009/ Accepted 22 July 2009

The fungal pathogen Cryptococcus neoformans causes approximately one million cases of cryptococcosis per year in people with AIDS. In contrast, the related species C. gattii is responsible for a much smaller number of cases, but these often occur in immunocompetent people. In fact, C. gattii has emerged in the last decade as the frequent cause of cryptococcosis in otherwise healthy people in British Columbia. We analyzed the immune responses elicited by three C. gattii strains and one C. neoformans strain in mice as a first step toward understanding why C. gattii is able to cause disease in immunocompetent hosts. The C. gattii strains all induced a less protective inflammatory response in C57BL/6 mice by inhibiting or failing to provoke the migration of neutrophils to sites of infection. The C. gattii strains also failed to elicit the production of protective cytokines, such as tumor necrosis factor alpha, compared to the ability of the C. neoformans strain. Despite these differences, the strain representing the major outbreak genotype from British Columbia showed a virulence equivalent to that of the C. neoformans strain, while two other C. gattii strains had reduced virulence. Taken together, our results indicate that C. gattii strains thrive in immunocompetent hosts by evading or suppressing the protective immune responses that normally limit the progression of disease caused by C. neoformans.

* Corresponding author. Mailing address: Michael Smith Laboratories, 2185 E. Mall, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z4. Phone: (604) 822-4732. Fax: (604) 822-2114. E-mail: kronstad{at}interchange.ubc.ca

{triangledown} Published ahead of print on 27 July 2009.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: A. Casadevall

Infection and Immunity, October 2009, p. 4284-4294, Vol. 77, No. 10
0019-9567/09/$08.00+0     doi:10.1128/IAI.00628-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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