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Title: Immune Evasion by Pathogenic Leptospira Strains: the Secretion of Proteases that Directly Cleave Complement Proteins
Authors: 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
Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Butantan Inst
Keywords: Leptospira
Immune Evasion
Innate Immunity
Complement System
Issue Date: 15-Mar-2014
Publisher: Oxford Univ Press Inc
Citation: Journal of Infectious Diseases. Cary: Oxford Univ Press Inc, v. 209, n. 6, p. 876-886, 2014.
Abstract: 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.
ISSN: 0022-1899
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Appears in Collections:Em verificação - Geral

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