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Eukaryotic Cell, April 2004, p. 413-419, Vol. 3, No. 2
1535-9778/04/$08.00+0     DOI: 10.1128/EC.3.2.413-419.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Challenge of Drosophila melanogaster with Cryptococcus neoformans and Role of the Innate Immune Response

Yiorgos Apidianakis,1,2 Laurence G. Rahme,1,2 Joseph Heitman,3,4,5 Frederick M. Ausubel,6,7 Stephen B. Calderwood,8,9 and Eleftherios Mylonakis8*

Department of Surgery,1 Department of Molecular Biology,7 Division of Infectious Diseases, Massachusetts General Hospital,8 Shriner's Burns Institute, Boston, Massachusetts 02114,2 Department of Genetics,6 Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115,9 Department of Medicine,3 Department of Molecular Genetics and Microbiology,4 Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 277105

Received 16 February 2004/ Accepted 20 February 2004

We found that the ingestion of Cryptococcus neoformans by Drosophila melanogaster resulted in the death of the fly but that the ingestion of Saccharomyces cerevisiae or the nonpathogenic Cryptococcus kuetzingii or Cryptococcus laurentii did not. The C. neoformans protein kinase A and RAS signal transduction pathways, previously shown to be involved in virulence in mammals, also played a role in killing Drosophila. Mutation of the Toll immune response pathway, the predominant antifungal pathway of the fly, did not play a role in Drosophila defense following ingestion of the yeast. However, the Toll pathway was necessary for the clearance of C. neoformans introduced directly into the hemolymph of D. melanogaster and for the survival of systemically infected flies.

* Corresponding author. Mailing address: Division of Infectious Diseases, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114-2696. Phone: (617) 726-3812. Fax: (617) 726-7416. E-mail: emylonakis{at}partners.org.

Eukaryotic Cell, April 2004, p. 413-419, Vol. 3, No. 2
1535-9778/04/$08.00+0     DOI: 10.1128/EC.3.2.413-419.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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