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Infection and Immunity, June 2003, p. 3190-3195, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3190-3195.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Expression of Multiple CPB Genes Encoding Cysteine Proteases Is Required for Leishmania mexicana Virulence In Vivo

Hubert Denise,1 Kathryn McNeil,2 Darren R. Brooks,1 James Alexander,2 Graham H. Coombs,3 and Jeremy C. Mottram1*

Wellcome Centre for Molecular Parasitology, The Anderson College, University of Glasgow, Glasgow G11 6NU,1 Department of Immunology, University of Strathclyde, Glasgow G4 0NR,2 Division of Infection and Immunity, Institute for Biomedical and Life Science, University of Glasgow, Glasgow G12 8QQ, United Kingdom3

Received 17 October 2002/ Returned for modification 14 January 2003/ Accepted 18 March 2003

Leishmania mexicana mutants deficient in the multicopy CPB gene array have reduced virulence, demonstrated by poor lesion growth in BALB/c mice and induction of a protective Th1 response. Reinsertion of the amastigote-specific CPB2.8 or metacyclic stage-specific CPB2 gene into a CPB-deficient mutant L. mexicana failed to restore either a Th2 response or sustained virulence. However, reexpression of multiple CPB genes from a cosmid significantly restored virulence. This was characterized by increased lesion and parasite growth and the acquisition of a Th2 response, as determined by measuring interleukin-4 production and immunoglobulin G1 (IgG1) and IgE levels. These studies confirm that L. mexicana cysteine proteases are important virulence factors and provide an explanation for the presence in L. mexicana of a multicopy tandem array of CPB genes.

* Corresponding author. Mailing address: Wellcome Centre for Molecular Parasitology, The Anderson College, University of Glasgow, Glasgow G11 6NU, United Kingdom. Phone: 44-141-330-3745. Fax: 44-141-330-5422. E-mail: j.mottram{at}udcf.gla.ac.uk.

Editor: J. M. Mansfield

Infection and Immunity, June 2003, p. 3190-3195, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3190-3195.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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