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Infection and Immunity, August 2009, p. 3491-3500, Vol. 77, No. 8
0019-9567/09/$08.00+0     doi:10.1128/IAI.00334-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Elucidating the Pathogenesis of Spores from the Human Fungal Pathogen Cryptococcus neoformans{triangledown}

Steven S. Giles,1,2 Taylor R. T. Dagenais,2 Michael R. Botts,1 Nancy P. Keller,2,3 and Christina M. Hull1,2*

Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin,1 Department of Medical Microbiology and Immunology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin,2 Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin3

Received 23 March 2009/ Returned for modification 24 April 2009/ Accepted 9 May 2009

Cryptococcus neoformans was first described as a human fungal pathogen more than a century ago. One aspect of the C. neoformans infectious life cycle that has been the subject of earnest debate is whether the spores are pathogenic. Despite much speculation, no direct evidence has been presented to resolve this outstanding question. We present evidence that C. neoformans spores are pathogenic in a mouse intranasal inhalation model of infection. In addition, we provide mechanistic insights into spore-host interactions. We found that C. neoformans spores were phagocytosed by alveolar macrophages via interactions between fungal β-(1,3)-glucan and the host receptors Dectin-1 and CD11b. Moreover, we discovered an important link between spore survival and macrophage activation state: intracellular spores were susceptible to reactive oxygen-nitrogen species. We anticipate these results will serve as the basis for a model to further investigate the pathogenic implications of infections caused by fungal spores.


* Corresponding author. Mailing address: 587 Medical Sciences Center, 1300 University Avenue, Madison, WI 53706-1510. Phone: (608) 265-5441. Fax: (608) 262-5253. E-mail: cmhull{at}wisc.edu

{triangledown} Published ahead of print on 18 May 2009.

Editor: A. Casadevall


Infection and Immunity, August 2009, p. 3491-3500, Vol. 77, No. 8
0019-9567/09/$08.00+0     doi:10.1128/IAI.00334-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Velagapudi, R., Hsueh, Y.-P., Geunes-Boyer, S., Wright, J. R., Heitman, J. (2009). Spores as Infectious Propagules of Cryptococcus neoformans. Infect. Immun. 77: 4345-4355 [Abstract] [Full Text]