Influence of parasite encoded inhibitors of serine peptidases in early infection of macrophages withLeishmania major
| Autor: | Sylvain C.P. Eschenlauer, Marilia S. Faria, Graham H. Coombs, Ana Paula C. A. Lima, Jeremy C. Mottram, Flávia L. Ribeiro-Gomes, George A. DosReis, Lesley S. Morrison, Nicolas Bland |
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| Rok vydání: | 2009 |
| Předmět: |
Serine Proteinase Inhibitors
Molecular Sequence Data Immunology Protozoan Proteins Leishmaniasis Cutaneous Microbiology Serine Mice 03 medical and health sciences Phagocytosis Virology medicine Animals Chymotrypsin Trypsin Leishmania major Amino Acid Sequence Amastigote 030304 developmental biology Mice Inbred BALB C 0303 health sciences biology Macrophages 030302 biochemistry & molecular biology Original Articles biology.organism_classification Leishmania 3. Good health Biochemistry Neutrophil elastase biology.protein Ecotin Leukocyte Elastase Sequence Alignment Gene Deletion medicine.drug |
| Zdroj: | Cellular Microbiology |
| ISSN: | 1462-5822 1462-5814 |
| DOI: | 10.1111/j.1462-5822.2008.01243.x |
| Popis: | Ecotin is a potent inhibitor of family S1A serine peptidases, enzymes lacking in the protozoan parasite Leishmania major. Nevertheless, L. major has three ecotin-like genes, termed inhibitor of serine peptidase (ISP). ISP1 is expressed in vector-borne procyclic and metacyclic promastigotes, whereas ISP2 is also expressed in the mammalian amastigote stage. Recombinant ISP2 inhibited neutrophil elastase, trypsin and chymotrypsin with K(i)s between 7.7 and 83 nM. L. major ISP2-ISP3 double null mutants (Deltaisp2/3) were created. These grew normally as promastigotes, but were internalized by macrophages more efficiently than wild-type parasites due to the upregulation of phagocytosis by a mechanism dependent on serine peptidase activity. Deltaisp2/3 promastigotes transformed to amastigotes, but failed to divide for 48 h. Intracellular multiplication of Deltaisp2/3 was similar to wild-type parasites when serine peptidase inhibitors were present, suggesting that defective intracellular growth results from the lack of serine peptidase inhibition during promastigote uptake. Deltaisp2/3 mutants were more infective than wild-type parasites to BALB/c mice at the early stages of infection, but became equivalent as the infection progressed. These data support the hypothesis that ISPs of L. major target host serine peptidases and influence the early stages of infection of the mammalian host. |
| Databáze: | OpenAIRE |
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