Immune Evasion by Pathogenic Leptospira Strains: The Secretion of Proteases that Directly Cleave Complement Proteins
| Autor: | Lourdes Isaac, Tatiana R. Fraga, Silvio Arruda Vasconcellos, Daniella dos Santos Courrol, Mónica Marcela Castiblanco-Valencia, Izaura Yoshico Hirata, Angela Silva Barbosa, Luiz Juliano |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Leptospira
Proteases Innate immune system biology Thermolysin Proteolytic enzymes Complement C3 biology.organism_classification Models Biological Complement factor B Recombinant Proteins Microbiology Complement system Infectious Diseases Immune system Bacterial Proteins Humans Immunology and Allergy Leptospirosis Secretion Complement Pathway Classical LEPTOSPIROSE Immune Evasion Peptide Hydrolases |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1537-6613 0022-1899 |
| Popis: | Leptospirosis is an infectious disease of public health importance. To successfully colonize the host, pathogens have evolved multiple strategies to escape the complement system. Here we demonstrate that the culture supernatant of pathogenic but not saprophytic Leptospira inhibit the three complement pathways. We showed that the proteolytic activity in the supernatants of pathogenic strains targets the central complement molecule C3 and specific proteins from each pathway, such as factor B, C2, and C4b. The proteases cleaved α and β chains of C3 and work in synergy with host regulators to inactivate C3b. Proteolytic activity was inhibited by 1,10-phenanthroline, suggesting the participation of metalloproteases. A recombinant leptospiral metalloprotease from the thermolysin family cleaved C3 in serum and could be one of the proteases responsible for the supernatant activity. We conclude that pathogenic leptospiral proteases can deactivate immune effector molecules and represent potential targets to the development of new therapies in leptospirosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|