title: Expression of multiple CPB genes encoding cysteine proteases is required for Leishmania mexicana virulence in vivo.
abstract: 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.
authors.affiliation: Wellcome Centre for Molecular Parasitology, The Anderson College, University of Glasgow, United Kingdom.
authors.forename: Hubert
authors.initials: H
authors.lastname: Denise
authors.forename: Kathryn
authors.initials: K
authors.lastname: McNeil
authors.forename: Darren R
authors.initials: DR
authors.lastname: Brooks
authors.forename: James
authors.initials: J
authors.lastname: Alexander
authors.forename: Graham H
authors.initials: GH
authors.lastname: Coombs
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Mottram
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan; D002401:Cathepsin B / Q000235:genetics*; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D015847:Interleukin-4 / Q000096:biosynthesis; D007894:Leishmania mexicana / Q000235:genetics / Q000472:pathogenicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D015800:Protozoan Proteins / Q000032:analysis; D018418:Th2 Cells / Q000276:immunology; D014774:Virulence
chemical_list: D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D015800:Protozoan Proteins; C093139:LACK antigen, Leishmania; D015847:Interleukin-4; D007073:Immunoglobulin E; D002401:Cathepsin B