Artigo
Immune Evasion by Pathogenic Leptospira Strains: the Secretion of Proteases that Directly Cleave Complement Proteins
Fecha
2014-03-15Registro en:
Journal of Infectious Diseases. Cary: Oxford Univ Press Inc, v. 209, n. 6, p. 876-886, 2014.
0022-1899
10.1093/infdis/jit569
WOS:000332343600009
Autor
Fraga, Tatiana Rodrigues
Courrol, Daniella dos Santos
Castiblanco-Valencia, Monica Marcela
Hirata, Izaura Yoshico
Vasconcellos, Slvio Arruda
Juliano, Luiz [UNIFESP]
Barbosa, Angela Silva
Isaac, Lourdes
Institución
Resumen
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 alpha and beta 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.