Leishmania major LACK antigen is required for efficient vertebrate parasitization.
J Exp Med
; 198(11): 1689-98, 2003 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-14657221
ABSTRACT
The Leishmania major LACK antigen is a key target of the immune response in susceptible BALB/c mice and remains a viable vaccine candidate for human leishmaniasis. We describe the genomic organization of the four lack genes in the L. major diploid genome together with results of selected lack gene targeting. Parasites containing a single lack gene in either the upstream or downstream locus grew comparably to wild-type promastigotes in vitro, but failed to parasitize BALB/c mice efficiently, even in a T cell-deficient environment. The replication of single copy lack mutants as amastigotes was attenuated in macrophages in vitro, and parasites failed to increase in numbers in immunodeficient mice, despite their persistence over months. Complementation with an additional lack copy was sufficient to induce robust lesion development, which also occurred using parasites with two lack genes. Conversely, attempts to generate lack-null parasites failed, suggesting that LACK is required for parasite viability. These data suggest that LACK is critical for effective mammalian parasitization and thus represents a potential drug target for leishmaniasis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Protozoários
/
Leishmania major
/
Antígenos de Protozoários
Limite:
Animals
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Estados Unidos